Natural Diabetes Cure and Treatment

Reverse Diabetes Now

Reverse Your Diabetes Today by Matt Traverso gives you instant, online access to a simple, step-by-step system in which Matt teaches you his powerful secrets, techniques, and unique treatment approach for quickly and easily eliminating pre-diabetes and Type 2 diabetes in as little as 21 days. The easy to implement concepts and techniques taught in the Reverse Your Diabetes Today system use simple, but highly effective diet and lifestyle changes to cleanse your body from harmful acids and heal your pancreas, allowing it to produce and regulate insulin naturally again. The diet advocated by the Reverse Diabetes book is not well known, but I have heard of it for at least 10 years. However, this diet, like all others, can only be good if you follow it. Funny how that works! Wouldnt it be great if we could just read about a diet and get its advantages? Read more here...

Reverse Diabetes Now Overview


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My Reverse Diabetes Now Review

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This is one of the best e-books I have read on this field. The writing style was simple and engaging. Content included was worth reading spending my precious time.

As a whole, this book contains everything you need to know about this subject. I would recommend it as a guide for beginners as well as experts and everyone in between.

Insulintreated type 1 diabetics IDDM

Patients must receive exogenous insulin to prevent ketoacidosis. B. Insulin can be given by sliding scale or continuous infusion. 1. Regular insulin 50 U 250 cc NS 0.2 units cc (flush IV tubing before starting). 2. Insulin rate in U hr blood glucose 150 (use 100 as denominator if patient is on steroids, or is markedly obese, or infected). Alternative dosing. 0.1 units kg hr. 3. An IV of D5W (1-1.5 ml kg hr) should be started prior to insulin. 4. Adjust insulin infusion as needed to keep glucose levels between 120-180 mg dL.

Enhanced Insulin Sensitivity

Water soluble compounds extracted from C. cassia potentiate insulin activity, as measured by glucose oxidation in the rat epididymal fat cell assay. The most active compound, methylhydroxy chalcone polymer (MHCP), increased glucose metabolism approximately 20-fold and was an effective mimetic of insulin according to an in vitro study. When combined with insulin, the responses were greater than additive, indicating synergism between the two compounds (Jarvill-Taylor et al 2001). According to Anderson, MHCP is actually a water-soluble polyphenols type-A polymer that increases insulin sensitivity by activating the key enzymes that stimulate insulin receptors, while inhibiting the enzymes that deactivate them. More specifically, extracts of cinnamon activate insulin receptor kinase and inhibit dephosphorylation of the insulin receptor, leading to maximal phosphorylation of the insulin receptor.

The Insulin Like Growth Factor Family

Evidence is accumulating that insulin-like growth factors (IGFs) may play an important role in breast carcinogenesis. The IGF family includes the polypeptide ligands IGF-I and IGF-II two receptors, IGF-IR and IGF-IIR six binding proteins (IGFBP-1 through IGFBP-6) and a large group of IGFBP proteases, which degrade IGFBPs to increase bioactive IGF. The actions of both IGF-I and IGF-II are mediated through IGF-IR, which is located on the cell membrane. The IGFs play an important role in regulating cell proliferation, differentiation, apoptosis, and transformation.62 As a potent mitogen, IGF-I increases DNA synthesis and accelerates the progression of cell division by stimulating the expression of cyclin D1.63

Noninsulindependent Type II diabetes mellitus

The incidence of non-insulin-dependent (i.e. Type II) diabetes mellitus (NIDDM) is increasing in adult urban populations around the world. The approximately 3 of adults currently affected by NIDDM will become an estimated 5 by 2025 (World Health Organization, 1998), as populations age and urbanize, and as obesity becomes more prevalent. NIDDM is a serious metabolic disorder which damages kidneys, heart, blood vessels and retina. The disorder results from ''insulin resistance'' - a reduction in the sensitivity of bodily tissues to insulin, the hormone which coordinates ''Thrifty genes'', and selective insulin resistance Almost a half-century ago, when obesity was much less prevalent than today, only a few populations (Pima Indians, Nauruans and other Polynesians, and Australian Aborigines) appeared to be particularly susceptible to diabetes. Further, the two main types of diabetes - adult-onset (NIDDM) and child-onset (insulin-dependent diabetes, IDDM distinguished by insufficient...

Glycaemic Control And Insulinsensitising Effect

Animal studies have indicated a potential for hypoglycaemic effects when used intravenously. Eleutherens A-G exert marked hypoglycaemic effects in normal and alloxan-induced hyperglycaemic mice (Hikino et al 1986) and eleutherosides show an insulin-like action in diabetic rats (Dardymov et al 1978). However, these effects have not been borne out in human studies (Farnsworth et al 1985) and may not relate to oral dosages of Siberian ginseng. A small, double-blind, randomised, multiple-crossover study using 12 healthy participants actually showed an increase in postprandial plasma glucose at 90 and 120 minutes when 3 g Siberian ginseng was given orally 40 minutes before a 75-g oral glucose tolerance test (Sievenpiper et al 2004). More recently, oral administration of an aqueous extract of Siberian ginseng was shown to improve insulin sensitivity and delay the development of insulin resistance in rats (Liu et al 2005). As a result further trials in people with impaired glucose tolerance...

Insulin regimens for type I diabetes

The most commonly used insulin injection preparations are the 'artificial' human insulins. Insulins are rapid-acting and short duration lispro insulin Starting insulin 2 It is important to use the simplest regimen for the patient and to provide optimal education about its administration and monitoring. Full replacement of insulin is achieved by using 2, 3 or 4 injections per day. Short-acting insulin before breakfast and lunch Intermediate- or long-acting insulin before evening meal Short-acting insulin before breakfast, lunch and dinner Intermediate-acting insulin at bedtime Insulin requirements often vary significantly even in the same individual under different lifestyle conditions. The new rapid-acting analogues can be taken with meals. Methods of giving insulin injections Fig. 17.2 Method of giving insulin injections use the abdomen Fig. 17.2 Method of giving insulin injections use the abdomen

Complications of diabetes

Complications may occur in both type I and type II diabetes even with early diagnosis and treatment (Fig 17.3). Insulin dependent diabetics still have a significantly reduced life expectancy. The main causes of death are diabetic nephropathy and vascular disease (myocardial infarction and stroke). Diabetes causes both macrovascular and microvascular complications but microvascular disease is specific to diabetes. Complications are illustrated in Figure 17.3 . Special attention should be paid to the 'deadly quartet' associated with type II diabetes. diabetic nephropathy unnary nfectlon Fig. 17.3 The complications of diabetes

Insulin Receptor Domain Structure

The insulin receptor (IR) is a glycosylated, disulfide-linked homodimer, with each monomer being made up of an a-chain that is entirely extracellular and a P-chain that spans the cell membrane once. The a-chain contains the insulin-binding determinants of the receptor, while the intracellular portion of the P-chain includes a protein-tyrosine kinase domain and domains involved in binding signal transduction proteins. The aP monomer of the IR is encoded by a gene with 22 exons alternative splicing of the IR pre-mRNA leads to the tissue-specific expression of two isoforms differing by the presence or absence of a 12-residue segment (exon 11) near the C terminus of the a-chain. The receptor is synthesized as a single chain with a 27-residue signal sequence and is glycosylated, oxidized to the disulfide form, and proteolytically processed to the two-chain form during transport to the cell surface. The mature a-chain of the human IR has 731 amino acid residues, while the P-chain has 620....

Insulin Signaling to Glucose Transport

A major, if not the major, endpoint of insulin signaling is the stimulation of glucose uptake (transport) in muscle and fat, the focus of the remainder of this chapter. Currently, at least two distinct pathways (Fig. 3) have been implicated in this process. Both pathways may be required for translocation of the insulin-regulated glucose transporter, GLUT4, a 12-transmembrane-spanning protein, from a vesicular storage compartment (GSV) within the cell, to the plasma membrane. Its insertion makes it competent to transport glucose into the cell (for reviews, see references 10 to 12 ). The most extensively characterized of these pathways begins with the IRS family of proteins (see Chapter 71). Tyrosine phosphorylation of these proteins by the insulin receptor provides recognition sites for Src homology domain 2 (SH2)-containing proteins. Of significance for several pathways in insulin action, including those leading to glucose transport and glycogen synthesis, is the binding and...

Diabetes Type 1 And Type

Orally, gymnema leaf is used to treat both type 1 and type 2 diabetes and hyperglycaemia. There are two clinical trials that suggest that gymnema may be useful in reducing blood glucose levels in both type 1 and type 2 diabetes. In one study the ability of the GS4 extract (400 mg day) to supplement the use of conventional oral hypoglycaemic agents (glibenclamide or tolbutamide) was studied in 22 patients with type 2 diabetes over 18-20 months. Treatment resulted in a significant reduction in fasting blood glucose (174 7 vs 124 5 mg dl_), HbA1c Gymnema sylvestre 675 vs 2.46 0.05 jg hexose mg protein) and raised insulin levels, whereas no changes were observed in the control group. This allowed for a decrease in conventional drug dosage and in five cases, blood glucose homeostasis was maintained with GS4 alone, suggesting that beta-cell function may have been restored (Baskaran et al 1990). In a second study, 27 type 2 diabetes patients were treated with 400 mg of an aqueous extract of...

Neonatal Transient Diabetes Mellitus

Neonatal transient diabetes mellitus (TNDM), with an incidence in newborns of 1 400,000 to 1 500,000 (Fosel, 1995 Shield et al., 1997), is characterized by intrauterine growth retardation, failure to thrive, hyperglycemia, glucosuria, dehydration, polyuria, occasional ketonemia and ketonuria, lethargy, and fever. Occasional features include anemia, macroglossia (Figure 1), and umbilical hernia. The diabetic condition may be permanent, subside to recur later as type 2 diabetes (Shield et al., 1997), or vanish completely (Christian et al., 1999).

IRSProteins and Insulin Signaling

Insulin and IGF1 receptors, like the receptors for other growth factors and cytokines, are composed of an extracellular ligand-binding domain that controls the conformation and activity of the intracellular tyrosine kinase 9,10 . Unlike most receptor tyrosine kinases that are activated upon ligand-induced dimerization, insulin and IGF1 receptors exist as inactive covalent dimers composed of two extracellular a-subunits and two transmembrane P-subunits. Insulin and IGF1 bind between the two a-subunits, thus inducing a conformation change that promotes tyrosine autophosphorylation on the cytoplasmic side of the adjacent P-subunits 11,12 . Autophosphorylation occurs in three distinct regions of the P-subunits, including the regulatory loop, the juxtamem-brane region, and the C-terminus. Phosphorylation of three tyrosine residues in the regulatory loop activates the tyrosine kinase by opening the catalytic domain to facilitate entry of adenosine triphosphate (ATP) and peptide substrates...

Lost In Darknes Depression Diabetes And Heart Disease

Source Diabetes Forecast. 56(5) 44-46. May 2003. Contact Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website Summary This article helps readers with diabetes to understand the problem of depression and the risks that having a chronic disease may contribute to any likelihood of experiencing depression. The author notes that depression may occur as a reaction to illness and changing social circumstances, such as after the onset of type 1 diabetes or a divorce, but depression also seems to have a genetic basis in some patients. The author briefly reviews the biological basis of depression, stress hormones, diagnosing

Agerelated Risk and Etiologic Factors for Diabetes Mellitus Type

Poor diet, genetic factors, obesity, and lack of exercise may partly explain the increased prevalence of glucose intolerance and type 2 diabetes with advancing age. Among the confounding factors for the development of type 2 diabetes associated with aging, the most important are increased body adiposity and reduced lean body mass. These changes are characteristic of the aging process, but individually can be found in many pathological states with similar untoward metabolic consequences. The concomitant occurrence of these body composition changes and aging per se probably has an important impact on the development of type 2 diabetes in elderly.

Pathogenesis of Diabetes Mellitus Type 2 in Relation to Aging

ALTERED INSULIN ACTION INSULIN RESISTANCE One factor clearly contributing to this age-related glucose intolerance is a decline with physiologic aging in sensitivity to the metabolic effects of insulin that is, the reduction of insulin sensitivity. This means a reduction in the activity of insulin on its target tissues such as muscle, liver, and adipose tissue. In the muscle this results in a decrease of glucose disposal. In the adipocytes this results in the inability of insulin to inhibit the lipolysis leading to the release of free fatty acids in the circulation. These FFAs in turn stimulate hepatic neoglucogenesis and VLDL secretion, reduce muscle glucose uptake, and may alter glucose-stimulated insulin secretion by beta cells. This age-related impairment of insulin action appears to be predominantly due to effects on the insulin signaling mechanism beyond the insulin receptor itself. However, the latter also may be involved to some extent (Fulop et al., 2003). In the liver the...

Relationship between Diabetes Mellitus and Aging in the Development of Cardiovascular Diseases

Development of atherosclerosis, as it is also for type 2 diabetes. Aging per se could present a state of impaired glucose tolerance due to the physiologic changes described. IGT is known to be a risk factor for progression to type 2 diabetes. Aging associated with the occurrence of type 2 diabetes increases several-fold the risk for development of cardiovascular diseases by approximately six to eight times more than aging alone (Nesto, 2003). This is due mainly to the strong occurrence of the classical, including hypertension, dyslipidemia, and nonclassical, including inflammatory cytokines, homocystein, and CRP risk factors. Altogether, the common pathway could be the insulin resistance and insulinopenia-induced hyperglycemia via the production of AGEs and oxidative stress.

Experimental Models Linking Diabetes Mellitus to Aging and Longevity

In some species, caloric restriction (CR) is associated with reduction of aging and increased longevity. It was observed that a reduced body size was correlated to an increased life span in mice, dogs, Caenorhabditis elegans, or Drosophila melanogaster. One very recent study could not find a clear general effect of body size on life span (Hafen, 2004 McCulloch et al., 2003). The question has been asked why smaller individuals would live longer. One explanation that has been put forward, mainly in invertebrates, is the homologous insulin IGF signaling (IIS). In C. elegans it was suggested that the IIS can act to limit the body size. However, in some wild-type strains this correlation was much less clear. Moreover, several mutations in C. elegans led to extended longevity phenotype. Among these are the genes involved in the insulin IGF-signaling pathway, such as daf-2 and age-1, or clk mutants related to respiratory metabolism. Similar results were obtained in Drosophila. The study in...

Mechanisms of Premature Aging in Diabetes

The clinical and phenotypic similarities between aging and diabetes suggest that there may be shared biochemical pathways leading to the tissue changes. Glucose is the principal metabolic fuel for many animal species. In general, with few exceptions, the plasma glucose level in various animals is maintained within a narrow range (60-140 mg dl). It is possible that the lower limit of blood glucose levels is determined by the minimum tissue requirements of metabolic fuel, and the upper limit defines the threshold beyond which glucotoxicity limits survival of the species (Mooradian and Thurman, 1999b). Avian species, especially owls and parrots, are the exception to this generalization. These animals have high blood glucose levels in the range of 250 to 350 mg dl and yet have a relatively long life expectancy and show no signs of classical diabetic complications. The overall constancy of blood glucose levels across a wide range of animal species suggests that hyperglycemia, except in...

Insulin Receptor Signaling

Insulin and insulin-like growth factor-1 (IGF-1) signaling pathways have been implicated in aging of several experimental organisms (Pardee et al., 2004). This pathway is critical to coordinating the influx of calories with the metabolic rate. Down-regulation of this pathway through caloric restriction is associated with increased life span in mice, worms, flies, and yeast (Barbieri et al., 2003). One of the key transcription factors implicated in aging, namely, FOXO, is regulated by insulin and IGF-1. The FOXO homolog in worms, DAF-16, has a central role in imparting longevity of worms with mutations in the insulin IGF-1 signaling pathway genes, such as daf-2 and age-1 (Kenyon et al., 1993). Over-expression of dFOXO in worms and DAF-16 in flies extends life span through interactions with a host of other nuclear receptors, particularly the PPARs (Giannakou et al., 2004 Henderson and Johnson, 2003). These receptors are up-regulated during caloric restriction, and overexpression of PPAR...

Type 2 diabetes the next global epidemic Definitions

In contrast to type 1 diabetes, which is known to result from autoimmune destruction of the insulin-secreting beta-cells of the pancreas, leading to lifelong dependence on exogenous insulin, the etiology of type 2 diabetes is poorly understood (Kahn, 2003). Whilst type 1 diabetes is typically diagnosed in childhood or early adulthood, type 2 diabetes classically presents in later life. These clinical distinctions lie behind previous disease classifications in which type 2 diabetes was known originally as maturity-onset diabetes, and subsequently, as non-insulin-dependent diabetes mellitus (World Health Organization Study Group, 1985). Under the most recent classification of diabetes subtypes, published in 1997 by a joint expert committee of the American Diabetes Association and the World Health Organization, individuals whose diabetes has an established basis - be that causal genetic variation (as in some monogenic forms of diabetes (see below)) or discrete environment risk factors...

Lessons from maturity onset diabetes of the young MODY

As mentioned earlier, a small proportion (around 1 ) of families with diabetes are clearly segregating an autosomal dominant form of early-onset T2D (Frayling et al., 2001). The term ''maturity onset diabetes of the young'' (MODY) was coined to describe these key clinical features, at a time when most diabetes seen before late middle age was autoimmune (that is, type 1, or juvenile-onset diabetes as it was then known). Most people with MODY were not particularly obese, suggesting that the predominant defect in this condition was likely to be beta-cell dysfunction rather than insulin resistance. Detailed clinical studies of MODY families pointed to significant heterogeneity between families with regard to disease progression and severity (Fajans, 1990 Tattersall andMansell, 1991). With the advent of modern positional cloning techniques, the availability of multigenerational families and the promise of penetrant disease alleles meant that MODY became an attractive target for gene...

The Regulation of GSK3 Activity by Insulin and Growth Factors

In embryonic stem cells that do not express 3-phospho-inositide-dependent protein kinase 1 (PDK1), an essential upstream activator of both PKB and MAPKAP-K1, the PKB-mediated inhibition of GSK3 (induced by insulin-like growth factor 1) and the MAPKAP-K1-mediated inhibition of GSK3 (induced by the tumor-promoting phorbol ester TPA) do not occur 26 . This genetic evidence supports the view that GSK3 can be inhibited by PKB and MAPKAP-K1 in vivo. Figure 1 GSK3 can be inhibited by several different agonists. The inhibition of GSK3 by growth factors, amino acids, and hormones, such as insulin, occurs by a different mechanism than does inhibition of GSK3 by Wnts. Protein kinases that are activated by these agonists, such as PKB, MAP-KAP-K1, and S6 kinase (S6K), phosphorylate the N terminus of GSK3 on a serine residue (Ser9 of GSK3P and Ser21 of GSK3a). In contrast, Wnt signaling does not lead to an increase in Ser9 Ser21 phosphorylation and instead may involve the displacement of Axin and...

Diabetes And Diabetic Nephropathy

Replacing animal protein with soy protein has been found to improve various disease markers in patients with type 1 or type 2 diabetes and people with obesity. In a RCT of 104 patients with type 2 diabetes, 12 months of a soy-based meal replacement was found to significantly improve weight loss, HbAlc and high-sensitivity C-reactive protein levels and significantly reduce the use of sulfonylureas and metformin compared to the use of individual diet plans (Li et al 2005). Another randomised trial involving 90 obese (non-diabetic) subjects suggests that 6 months on a low-fat, high-soy-protein diet can help to reduce fat while preserving muscle mass and improving glycaemic control and the lipid profile (Deibert et al 2004). studies of diabetic nephropathy. In a controlled crossover trial, 8 weeks of substituting soy protein for animal protein significantly reduced glomerular filtration rates in 12 young adults with type 1 diabetes mellitus (Stephenson et al 2005). In another crossover...

NCEPDefined Metabolic Syndrome Diabetes and Prevalence of Coronary Heart Disease Among Nhanes Iii Participants Age 50

May 2003. Contact Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website Summary Although the individual components of the metabolic syndrome are clearly associated with increased risk for coronary heart disease (CHD), the authors of this study wanted to quantify the increased prevalence of CHD among people with metabolic syndrome. The authors used the Third National Health and Nutrition Examination Survey (NHANES III) to categorize adults over 50 years of age by presence of metabolic syndrome, with or without diabetes. Metabolic syndrome is very common, with approximately 44 percent of the united States population over 50 years of age meeting the criteria. in contrast, diabetes without metabolic syndrome is uncommon (13 percent of those with diabetes). Older Americans over 50 years of age without metabolic syndrome, regardless of diabetes status, had the lowest CHD...

Diabetes and Pregnancy

Pregnancies complicated with gestational diabetes have an increased risk of maternal and perinatal complications, long-term maternal morbidity, and morbidity to the offspring. The causes of perinatal morbidity are neonatal hypoglycemia, hyperbilirubinemia, hypocalcemia, polycythemia, macrosomia birth weight more than 9 lbs (or 4 kg), and with that the problem shoulder dystocia, an abnormal apgar score, and Erb's palsy. Family history of diabetes

Diagnosis of gestational diabetes

The diagnosis of gestational diabetes is usually accomplished early in the third trimester of pregnancy. The one-hour glucola test is the screening test for gestational diabetes. Nonfasting women are given 50 grams of glucose in a flavored solution, and their blood is taken one hour after ingestion. If the blood sugar equals or exceeds 140 mg dL, then women are asked to take a three-hour glucose tolerance test (GTT). B. For the three-hour GTT, women are advised to consume an unrestricted diet containing at least 150 grams of carbohydrates daily three days prior to testing. They are asked to fast for 10-14 hours prior to testing. All tests are performed in the morning. Blood is drawn fasting and at 1, 2, and 3 hours postingestion of a 100-gram glucose-containing solution. If any two (out of 4) or more results are abnormal, then they are diagnosed as having gestational diabetes. Criteria for Gestational Diabetes Any two or more abnormal results are diagnostic of gestational diabetes.

Heart Disease and Diabetes

January 2003. Contact Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website Summary This brief fact sheet reminds readers of the connection between heart disease and diabetes. The fact sheet notes that many conditions that increase one's changes of getting heart disease are more common in people with diabetes. These conditions include cholesterol problems, high blood pressure (hypertension), overweight, and blood clotting problems. Heart attacks, known in the medical community as myocardial infarctions, are one of the most common heart conditions. For most people, a heart condition leads to symptoms such as chest pain or pressure, jaw pain, arm pain, shortness of breath, sweating, and pounding heartbeat. However, many people with diabetes and heart disease do not notice any symptoms at all. This is called silent ischemia. Silent ischemia is very dangerous because...

Changes In Growth Hormone And Insulinlike Growth Factor1 In Hiv Infection

Disturbances in the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) axis have also been described in HIV infection. Decreased levels of IGF-1 have been noted in some malnourished individuals with HIV infection (37,38), but normal levels of IGF-1 were reported in two other groups of patients with prior weight loss (30,39). One potential explanation for these discrepant findings is that the patients in these latter two groups were studied during periods of relative clinical and weight stability, whereas the two former groups included patients who were losing weight at the time of study.

Insulinlike Growth Factor1 Igf1

Overall, the nitrogen-retaining effects of rhIGF-1 in metabolic ward studies did not consistently attain levels seen with rhGH (30), whereas the increases in REE were comparable to those seen with rhGH. Moreover, the insulin-like effect of IGF-1 poses a potential obstacle to its use in patients with HIV-associated wasting, many of whom may be at increased risk of hypoglycemia because of limited energy stores, anorexia, malabsorption, or increased insulin sensitivity (54,55).

Insulinlike Growth Factor Axis Components

Mature IGF-I and IGF-II are single-chain polypeptides of 70 and 67 amino acids, respectively, with 62 overall sequence identity (4-5). Due to structural identity with insulin, the IGF polypeptide chain has been divided into four domains arranged as B-C-A-D. IGF A- and B-domains have 45 sequence identity with insulin A- and B-chain however, the connecting peptide C is shorter than the proinsulin C-chain, and the carboxyl-terminal D-domain extension is exclusive to IGF. Another parallel between IGF and insulin structure is the presence of three intrachain disulphide bonds arranged in the same disposition as in insulin, i.e., two connecting B- and A-domains and one intra-A-domain (6). Moreover, the IGF are synthesized as preproproteins with signal peptides of about 25 amino acids at the N-terminus of the B-domain, and further extensions of 35-85 residues at the C-terminus of the D-domain, termed the E-peptide (7). Although the signal peptide and E-domain are deleted sequentially by...

Gsk3 And Insulin Resistance

GSK-3, one of the final regulatory proteins in glycogen production, is an attractive target for non-insulin-dependent diabetes mellitus (NIDDM). In NIDDM biopsy tissue GSK-3 activity is inversely correlated to glycogen synthase activity implicating GSK-3 as contributing to insulin resistance 27,28 . Insulin and insulin receptors are expressed in the brain, including the medial temporal regions that support the formation of memory 29 . Some NIDDM patients are also afflicted with verbal and visual memory decline independent of clinically diagnosed dementia 30 . More recently evidence suggests that the insulin resistance known to underlie NIDDM may also contribute to the clinical symptoms of Alzheimer's disease. GSK-3 intersects these two diseases, and therapeutic inhibition of GSK-3 is indicated for both.


Three systemic reviews of herbal medicines for glycaemlc control In diabetes found that Aloe vera can lower blood glucose levels In diabetic patients (Grover et al 2002, Vogler & Ernst 1999, Yeh et al 2003). In one trial aloe juice consisting of 80 gel or placebo was given In a trial of 40 patients who were recently diagnosed with type 1 diabetes at the dose of 1 tablespoon twice dally. From day 14 the blood sugar levels In the aloe group began to fall significantly compared with the control group and Aloe vera 27 levels were also substantially reduced but cholesterol levels remained the same (Yongchalyudha et al 1996). A single blind, placebo-controlled trial found that oral aloe gel was more effective in reducing blood sugar levels when combined with glibenclamide than glibenclamide alone in 72 patients with type 2 diabetes. Patients took 5 mg of glibenclamide twice daily and 1 tablespoon aloe gel. Fasting blood glucose levels dropped appreciably after just 2 weeks' treatment,...

Insulin And Gsk3

In 1960 Joseph Larner reported that the activity of glycogen synthase was increased within minutes when rat diaphragms were incubated with insulin 11 and, a few years later, he showed that this resulted from decreased phos-phorylation of this enzyme 12 . Following the discovery that PKA can phos-phorylate and inhibit GSK-3 in vitro 13,14 , it was thought that insulin must exert its effect on glycogen synthase by inhibiting PKA, but no decrease in the concentration of cyclic AMP could be detected in muscle under conditions where insulin stimulated glycogen synthase 12 . This led Joe Larner to suggest that insulin might trigger the formation of a second messenger or chemical mediator distinct from cyclic AMP, which bound to PKA and prevented its activation by cyclic AMP but, despite much effort, no such molecule was ever purified and characterised. However, when other glycogen synthase kinases were identifieid, I suggested that insulin might instead activate glycogen synthase by...


5-alpha-aldose inhibition Diabetic patients may accumulate intracellular quantities of the sugars sorbitol and dulcitol, because of an increase in the polyol pathway involving the enzyme 5-alpha-aldose. Oral baicalin and liquid extract of licorice (also rich in flavonoids) reduced the sorbitol levels in the red blood cells of diabetic rats (Lin et al 1980, Zhou & Zhang 1989). Alpha-glucosidase inhibition Alpha-glucosidase inhibitors (e.g. acarbose) are a class of oral medicine for type 2 diabetes, which blocks the enzymes that digest starches in food. The result is a slower and lower rise in blood glucose throughout the day, especially immediately after meals. Methanol extracts of Scutellaria balcalensls, Rheum officinale and Paeonia suffruticosa showed potent inhibitory activity against rat intestinal sucrase. The active principles were identified as baicalein and methyl gallate (from the latter two plants). In addition to its activity against the rat enzyme, baicalein also...

Diabetes Mellitus

Debate exists regarding the heights of children and adolescents with newly diagnosed Type 1 diabetes mellitus (IDDM) (32-34), however, it appears that growth deceleration may be seen prior to islet cell failure and overt symptoms of diabetes (35). Further, poor metabolic control of IDDM is associated with chronic elevation of serum GH concentration, growth retardation, and delayed sexual development (36,37). The metabolic effects of the elevated GH concentrations have been implicated as a causative factor in the development of diabetic retinopathy and other microvascular complications (38). In 52 adolescents with IDDM, GH secretory dynamics and IGF binding proteins (IGFBPs) were assessed during puberty (39). Subjects were divided into two separate groups based on glycemic control. Using overnight GH sampling studies, no significant differences were found in the two groups with respect to total GH secretion, number of GH pulses, or GH peak amplitude. The data were similar to that seen...

Insulin Resistance

Insulin resistance is a common condition and can be seen, for example, in NIDDM, obesity, and hypertension. The inter-relationship between insulin resistance and these conditions, as well as the exact mechanisms for insulin resistance, have not yet been fully clarified. It has recently been clear that GH-deficient adults are also insulin resistant in peripheral tissues (as measured using the hyperinsulinemic euglycemic clamp technique 67,68 ). In our study, glucose disposal rate (GDR) in the GH-deficient group was less than half that of controls, when calculated according to body weight and when corrected for body fat (67). The decreased lean body mass and the increased abdominal obesity in GH deficiency may be of importance for this finding as the association between increased body fat mass and insulin resistance is stronger in the presence of abdominal obesity (69). Low levels of serum IGF-1 may also contribute to insulin resistance (70) as IGF-1 stimulates the glucose transport in...

Diabetes Assessment

Diabetes affects millions of people worldwide. It is a leading cause of death, and as a result, is a large area of study. Diabetes is actually a group of diseases characterized by aberrant glucose metabolism. Type I or insulin-dependent diabetes results from immune-mediated destruction of pancreatic beta-cells. Type II or noninsulin-dependent diabetes results in hyperglycemia without loss of endogenous insulin reserve or loss of pancreatic islets. Thus, Type II diabetes is characterized by the presence of insulin resistance, which is often associated with obesity and advancing age and accounts for most cases of diabetes. The use of mouse models and transgenic technology has been important in the understanding of this complex disease.42 Clinically, overt diabetic symptoms include polyuria, polydypsia, and weight loss. One easy pheno-typing assay is monitoring for glucose in the urine. This test should be performed weekly on at-risk mice. Many other phenotyping procedures and tests have...

Preventing Diabetes

Nicotinamide has been proposed as a useful therapeutic agent for the prevention of type 1 diabetes and also as an adjunct to intensive insulin therapy (Pocoit et al 1996). Interestingly, nicotinamide has also been shown to cause insulin resistance resulting in increased insulin secretion in healthy subjects with a family history of type 1 diabetes (Greenbaum et al 1996). A concern therefore exists that monitoring such people for signs of development of the disease may be complicated by the use of nicotinamide. 2007 Elsevier Australia Protects beta-cells Type 1 diabetes is characterised by progressive beta-cell destruction, which leads to complete insulin deficiency at the time of diagnosis 80-90 of beta cells have been destroyed (Virtanen & Aro 1994). Nicotinamide has been shown to protect beta-cells from inflammatory insults and to improve residual beta-cell function in patients after onset of type 1 diabetes (Gale 1996, Lampeter et al One RCT using 25 mg kg versus 50 mg kg...

Type I Diabetes

The characteristic dysfunction is the destruction of pancreatic beta cells that produce insulin. This results clinically in hyperglycemia, ketoacidosis, and exogenous insulin dependence. Long-term clinical effects include neuropathy, retinopathy leading to blindness, and nephropathy leading to kidney failure. B. Type I diabetes demonstrates an association with the highly polymorphic human leukocyte antigen (HLA) class II genes that play a role in the immune response. The specific loci involved in Type I diabetes are called HLA-DR3 and HLA-DR4 loci they are located on the short arm (p arm) of chromosome 6 (p6). E. Markers for immune destruction of pancreatic beta cells include autoantibodies to glutamic acid decarboxylase (GAD65), insulin, and tyrosine phosphatases 1A 2 and

Ginseng And Diabetes

The value of ginseng preparations in the treatment of diabetes mellitus is debatable. Diabetes, diabetes mellitus or sugar diabetes, is a common condition occurring worldwide and amongst all classes of people but more frequently amongst the poor and the aged in modern industrialised communities. In such societies it is rated as the third most common cause of death after cancers and cardiovascular conditions. The disease is characterised by impaired carbohydrate metabolism caused by inadequate production in the pancreatic islets of Langerhans of the hormone insulin, a small protein molecule (molecular weight 5808) comprising two amino acid chains connected to each other by disulphide linkages. In the absence of insulin in the blood stream the blood sugar level rises abnormally (hyperglycaemia) and sugar passes readily into the urine with resultant glucosuria or polyuria. Such rapid liquid excretion leads in turn to the characteristic thirst of diabetics. Lack of insulin may also be due...

History and Physical Examination

Past Medical History (PMH) Past diseases, surgeries, hospitalizations medical problems history of diabetes, hypertension, peptic ulcer disease, asthma, myocardial infarction, cancer. In children include birth history, prenatal history, immunizations, and type of feedings.

Genetic Basis Of Hormonal Carcinogenesis

And some of these are eventually relevant to the constellation of such mutations needed to produce the malignant phenotype. Ovarian steroid hormones drive the process of cell division directly and are, thus, the primary carcinogens. The amount of ovarian steroid hormones produced during each menstrual cycle is under strong genetic control, and the relevant genes are those in the relevant sex steroid biosynthesis and metabolism pathway (Table 1.1). We assume that there are common (> 1 ) sequence variations in these genes, which can produce meaningful differences in total ovarian steriod exposure over a woman's lifetime. Of course, the same, or novel, sequence variants in these genes can be associated with the progression of hormone-related cancers, as has been well documented for variants in the androgen receptor gene.20 The details of the endocrine pathways and the relevant candidate genes will be discussed by several of the chapters in this book, so further details are not provided...

Classification systems

Classification systems include categorical, dimensional, and multiaxial types. In the categorical type of classification, each case is allocated to one of several mutually exclusive groups. This simple method is the most suitable one for clinical settings. Categorical systems are usually used in a hierarchical way, so that each case receives only one main diagnosis. Organic psychoses take precedence over functional psychoses, and functional psychoses over neuroses. This can lead to oversimplification of complex cases, and does not take account of 'comorbidity', in which two psychiatric diagnoses (for example, anxiety state and alcohol misuse) or a physical and a psychiatric diagnosis (for example, diabetes and depression) coexist.

The Unusual Substrate Specificity Of Gsk3

Although GSK-3 was originally identified as a protein kinase involved in the regulation of glycogen metabolism, we now know that it participates in the control of many cellular processes, including embryonic development, where it is a key component of the Wnt signalling pathway, as well as gene transcription and neuronal cell function, which will be apparent from reading the chapters in this book. Undoubtedly, many more substrates for GSK-3 remain to be discovered in these and other processes. Another extremely exciting development in recent years has been has the advent of potent and specific inhibitors of GSK-3, which have not only become powerful pharmacological reagents with which to study its functions, but also have therapeutical potential for the treatment of diabetes, stroke, Alzheimer's and other diseases. These aspects are the major topic of Sections B and C of this book. However, these compounds are still at the preclinical stage and whether inhibitors of GSK-3 can be used...

History and Uses of Plant Biotechnology

It is now a routine practice to combine, exchange or mix genetic material. If thought useful, DNA can be isolated from one organism, combined with DNA from another (so called recombinant DNA) and placed into cells of a third organism. As a result, it is for example possible to have bacterial cells produce human proteins, such as human insulin. Therapeutic compounds (e.g. interferon, inter-leukin) that were unavailable previously can now be synthesised in a variety of systems, ranging from micro-organisms to plant or animal cells. Biotechnology can be also used to produce artificial transplant materials such as blood-vessel or skin tissue. Basic knowledge, as well as novel pharmaceuticals from biological origin, contribute significantly in treatments for cardiovascular diseases, cancer, stroke, etc. Biotechnology is also applied in other areas such as the environment and food. Micro-organisms have been used to efficiently extract minerals from ores and to clean up pollutants....

Janet Franklin BMed SciHons MNutr Diet

Professor, Department of Physiology, and Director, Obesity and Diabetes Research Center, University of Maryland, Baltimore, Maryland, U.S.A. Hans Hauner, M.D. Professor, Clinical Department, German Diabetes Research Institute, Dusseldorf, Germany Rudolph L. Leibel, M.D. Professor and Head, Division of Molecular Genetics, Department of Pediatrics, and Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, New York, U.S.A. F. Xavier Pi-Sunyer, M.D. Professor and Director, Division of Endocrinology, Diabetes, and Nutrition, Columbia University College of Physicians and Surgeons, and St. Luke's-Roosevelt Hospital Center, New York, New York, U.S.A.

Psychiatric Disorders

After the introduction of classic physiologic methods to the study of the forebrain, interest turned to how the results of these studies could be applied to the clinical realm. Because of the horrid conditions within psychiatric facilities at the time and the primitive nature of nonsurgical therapies (e.g., insulin and electric shock), the advent of psychosurgery held great promise. Stereotactic variants of psychosurgical procedures have included cingulot-omy 28 , anterior capsulotomy 29 , tractotomy 30 , and others.

Epidemiology Of Sexual Dysfunction

Numerous population surveys in this and other countries indicate a high prevalence of sexual problems in the general population. These surveys indicate that 40 of women have evidence of psychosexual dysfunction. The corresponding number for men is 30 (25). We have more evidence concerning the prevalence of sexual problems in men than women although the data base in both groups is rapidly growing. Correlates of erectile dysfunction in men include diabetes, vascular disease, age, and cigarette smoking. Serum dehydroepiandro-sterone and high-density lipoprotein cholesterol were found to be negatively correlated with erectile problems (26). Depression was correlated with erectile function in cross sectional studies, whereas passive personality traits tended to predict who would develop impotence in a prospective study (27). Studies in other countries have, in general, found somewhat similar rates of erectile dysfunction in the same age population and also that erectile dysfunction tends...

General Considerations of Hormones

The study of endocrinology over the past century quite naturally has been dependent upon the scientific methodologies available to probe the various endocrine systems. Thus, in the interval 1900-1960, endocrinology was largely pursued at the physiological level. This resulted in the discovery of approximately 25 hormones the detail of specification of the hormone structure was usually inversely proportional to the size of the hormone. Accordingly, the complete structure of thyroxin (molecular weight 770) was defined in 1926, while the sequence and structure of the small protein hormone insulin would not be obtained until 1953 (amino acid sequence) and 1969 (three-dimensional structure).

Case Detection Outbreak Detection and Outbreak Characterization

A clinician establishes a diagnosis by collecting and interpreting diagnostic data, including symptoms, physical observations (e.g., rash or temperature), risk factors for disease (e.g., travel to a foreign country), pre-existing diseases in the individual (e.g., diabetes), results of microbiological tests, radiographic examinations, and autopsy findings. The interpretation of diagnostic data is a complex cognitive activity. The clinician first generates a differential diagnosis, which is a list of diseases that the patient could have given the information the clinician has thus far. The clinician then resolves the differential

Nonneoplastic Conditions

Infective oesophagitis may be seen in otherwise healthy individuals but is more commonly encountered where there is alteration of either local or systemic immunity (e.g., AIDS). Underlying ulceration, broad-spectrum antibiotics, diabetes, corticosteroid therapy and immunosuppressive drugs can all alter the local gut flora resulting in superimposed infection. Causative agents are candidal fungus, herpes simplex virus (HSV 1 and 2), cytomegalovirus (CMV), and atypical mycobacteria.

Of Overweight Patients

Overweight is now recognized as a risk factor for cardiovascular disease and as a contributing factor in the development of other diseases, most notably diabetes and gallbladder disease. In this context, it is important to evaluate and treat the obesity and other risk factors so as to reduce the overall likelihood for developing disease and to reduce the social consequence of being obese. The clinician or therapist who sees an overweight patient needs to obtain certain basic information which is relevant to assessing its risk (Table 9) (100-108). This includes an understanding of the events that led to the development of obesity, what patients have done to deal with the problem, and how successful and unsuccessful they were in these efforts. Several of these items are listed in Table 10. The family constellation is important for identifying attitudes about obesity and the possibility of finding rare genetic causes. Information about the amount of weight gain (> 20 lb or > 10 kg)...

TABLE 5 Extraglandular Manifestations in Primary SS

Diagnosis of SS also requires exclusion of other conditions that can mimic it. These include previous radiation therapy to the head and neck, amyloidosis, sarcoidosis, lymphoma, graft versus host disease, hepatitis C virus infection, HIV-diffuse infiltrative lymphocytosis syndrome, medication-induced dryness, and uncontrolled diabetes mellitus.

Abnormal Involuntary Movement Scale

Tardive dyskinesia is a syndrome characterized by abnormal involuntary movements of the patient's face, mouth, trunk, or limbs, which affects 20 -30 of patients who have been treated for months or years with neuroleptic medications. Patients who are older, are heavy smokers, or have diabetes mellitus are at higher risk of developing TD. The movements of the patient's limbs and trunk are sometimes called choreathetoid, which means a dance-like movement that repeats itself and has no rhythm. The AIMS test is used not only to detect tardive dyskinesia but also to follow the severity of a patient's TD over time. It is a valuable tool for clinicians who are monitoring the effects of long-term treatment with neuroleptic medications and also for researchers studying the effects of these drugs. The AIMS test is given every three to six months to monitor the patient for the development of TD. For most patients, TD develops three months after the initiation of neuroleptic therapy in elderly...

Chest Pain and Myocardial Infarction

Cardiac Risk factors Hypertension, hyperlipidemia, diabetes, smoking, and a strong family history (coronary artery disease in early or mid-adulthood in a first-degree relative). PMH History of diabetes, claudication, stroke. Exercise tolerance history of peptic ulcer disease. Prior history of myocardial infarction, coronary bypass grafting or angioplasty.

Brainstem Malignant Glioma Subtypes

The initial neurologic symptoms often respond partially with the use of dexamethasone or another corticosteroid, although the improvement in function is temporary. The dose of steroids is not standardized and should be the minimal dose necessary to control symptoms. Children may require steroid therapy for weeks to months, therefore monitoring of blood pressure and blood sugar is recommended. Although not routinely practiced, the use of prophylactic antibiotic therapy (usually trimethoprim + sulfamethoxazole or pentamidine) may be considered for prevention of pneumocystis pneumonia. The risk of gastric ulceration needs to be considered, and although the use of proton pump inhibitors, H2-blockers, or buffering agents has not been proven to decrease the risk of ulceration, they are commonly used.

Perioperative betaadrenergic blockade

Eligibility is determined by the presence of any two minor criteria (age greater than 65, hypertension, current smoker, cholesterol greater than 240 mg dL, or non-insulin dependent diabetes) or any single major criterion (high-risk surgical procedure, history of transient ischemic attack or stroke, insulin dependent diabetes, or chronic renal insufficiency)

Mechanism Of Hormonal Action

Most peptide hormones do not require entry into the cytoplasm of their target cells to initiate a biological response since the ligand-binding domain of the receptor exists on the outer surface of the target cell (see Figure 1-22). As discussed in relation to Figure 1-20, some peptide hormones (e.g., insulin and nerve growth factor), when bound to their receptor, are subjected to endocytosis and are moved into the interior of the cell.

The Ill Prepared Study

The responsibility for patient preparation lies mainly with the referring physician. If the patient is restless and unable to cooperate, sedation must be considered. Special preparatory measures have to be communicated and explained to the patient with sufficient care, making sure that the information is understood. A lady undergoing an ultrasound of the abdomen, for example, should preferably be fasting because an air-filled stomach hinders optimal visualization of the pancreas. A nervous older gentleman who is scheduled for an upper gastrointestinal study with barium and air followed by a small-bowel follow-through should also be fasting to allow for a good contrast coating of the gastric mucosa. Fasting in this context means no breakfast, no coffee, no smoking, no tooth-brushing and, of course, no alcohol. For obvious reasons, the study should be scheduled in the morning hours and diabetic patients should be examined first and perhaps need to consider reducing their morning dose of...

Role Of Wnt Signaling And Gsk3 In Development

During Xenopus embryonic development GSK-3 acts as a negative regulator of dorsal axis formation 8 . Inhibition of GSK-3 activity leads to stabilization of P-catenin and expression of target dorsalizing genes 9,10 . GSK-3 promotes P-catenin phosphorylation, which stimulates its degradation by the ubiquitin-proteasome system 11 . Maternally expressed P-catenin is essential for dorsal determination and is localized to the future dorsal side of the embryo just after egg fertilization 12,13 . Thus meiotic maturation can be considered as a preparation for asymmetric localization of P-catenin and dorsal axis formation. Interestingly insulin, as well as progesterone, can promote meiotic maturation of Xenopus oocytes.

Pancreas Ampulla of Vater and Extrahepatic Bile Ducts

The pancreas is a soft, lobulated retroperitoneal organ which is both an endocrine and exocrine gland. The exocrine portion produces enzymes (lipases, proteases) which are conveyed to the duodenum by the pancreatic duct and are concerned with digestion. The endocrine portion (including the islets of Langerhans) produces hormones such as insulin and glucagon. The pancreas is subdivided as follows (Figure 3.1)

Haemostatic genetic risk factors in arterial thrombosis

Heart disease, diabetes, and many cancers probably arise from the interaction of acquired and genetic factors. For arterial thrombotic diseases, such as, myocardial infarction and stroke a number of environmental risk factors are well-established, including smoking, diet, dyslipidaemia, hypertension, and impaired glucose metabolism. The role of haemostatic disorders in the development of arterial thrombosis is emerging.68--75 Arterial thrombogenesis results from atherosclerosis and thrombosis, while atherosclerosis is a disease of the vessel wall resulting from chronic changes in vessel wall cellular components, occurring gradually over many years. The thrombotic event is an acute event thought to be triggered by tissue factor interaction with factor Vila and almost certainly influenced by haemostatic factors, such as, fibrinogen, fibrinolytic factors, and platelet activation.86--88 How the atherosclerotic process might be influenced by haemostatic factors is less clear.72,77

Sanger Was The First To Determine The Sequence Of A Polypeptide

Mature insulin consists of the 21-residue A chain and the 30-residue B chain linked by disulfide bonds. Frederick Sanger reduced the disulfide bonds (Figure 4-3), separated the A and B chains, and cleaved each chain into smaller peptides using trypsin, chymotrypsin, and pepsin. The resulting peptides were then isolated and treated with acid to hydrolyze peptide bonds and generate peptides with as few as two or three amino acids. Each peptide was reacted with 1-fluoro-2,4-dinitroben-zene (Sanger's reagent), which derivatizes the exposed a-amino group of amino terminal residues. The amino acid content of each peptide was then determined. While the e-amino group of lysine also reacts with Sanger's reagent, amino-terminal lysines can be distinguished from those at other positions because they react with 2 mol of Sanger's reagent. Working backwards to larger fragments enabled Sanger to determine the complete sequence of insulin, an accomplishment for which he received a Nobel Prize in 1958.

Applications Of Microarrays To Agingrelated Research

Several studies have reported gene expression profiles corresponding to long-lived mammalian models, as a result of environmental changes such as calorie restriction (CR) (Park and Prolla, 2005b), as well as longevity-enhancing mutations, such as the Ames dwarf, the growth hormone receptor knock-out (GHR-KO) (Dozmorov et al., 2001 Miller et al., 2002 Tsuchiya et al., 2004), and the fat-specific insulin receptor knock-out (FIRKO) (Bluher et al., 2004). In C. elegans, the transcriptional changes associated with longevity-determining mutations in the insulin-like IFG-1 pathway have been well characterized by microarray, resulting in the identification of several previously unknown aging genes (McElwee et al., 2003 Murphy et al., 2003).

The Realities Of Overweight

Overweight, central or abdominal fat, weight gain after age 20, and a sedentary lifestyle all increase health risks and increase economic costs of obesity. Intentional weight loss by overweight individuals, on the other hand, reduces these risks. Although data are not yet available, researchers widely believe that long-term intentional weight loss lowers overall mortality, particularly from diabetes, gallbladder disease, hypertension, heart disease, and some types of cancer.

Facilitated Diffusion

Most sugars and amino acids are insoluble in lipids, and they are too large to pass through cell membrane pores. Facilitated diffusion includes not only protein channels, but also certain proteins that function as carriers to bring such molecules across the cell membrane. In the facilitated diffusion of glucose, for example, glucose combines with a protein carrier molecule at the surface of the membrane. This union of glucose and carrier molecule changes the shape of the carrier that moves glucose to the inner face of the membrane. The glucose portion is released, and the carrier molecule can return to its original shape to pick up another glucose molecule. The hormone insulin, discussed in chapter 13 (p. 531), promotes facilitated diffusion of glucose through the membranes of certain cells.

Neoplastic Conditions

Pancreatic endocrine tumours single or multiple and forming a minority of pancreatic tumours they can be small (< 1-2 cm), well circumscribed and pale or yellow in colour. They are positive for general neuroendocrine markers (chromogranin, synaptophysin) and specific peptides, e.g., insulin, glucagon, gastrin. Many (60-85 ) are associated with a functional hormonal syndrome, e.g., Zollinger-Ellison syndrome due to pancreaticoduodenal gastrinomas. The pancreas is also involved in 80-100 of type I multiple endocrine neoplasia (MEN) syndrome comprising hyperplasia or tumours of parathyroid, pituitary, adrenal glands and pancreas (usually gastrinoma). Histology does not reliably predict behaviour and better indicators of potential malignancy are functionality and established metastases - insulinoma (85 benign), gastrinoma (60-85 malignant), size > 3 cm, site (e.g., duodenal), invasion of vessels, nodes, adjacent organs and liver.

ART 2005 1 Perspective

In June 1997, the FDA published the first warning about the development of diabetes mellitus associated with the use of PIs (Ault 1997). In February 1998, the CROI in Chicago finally brought home the realization among clinicians that protease inhibitors were perhaps not as selective as had long been believed. One poster after the next, indeed whole walls of pictures showed fat abdomens, buffalo humps, thin legs and faces. A new term was introduced at the beginning of 1998, which would influence the antiretroviral therapy of the years to come lipodystrophy. And so the old medical wisdom was shown to hold true even for HAART all effective drugs have side effects. The actual cause of lipodystrophy remained completely unclear. Then, in early 1999, a new hypothesis emerged from the Netherlands mitochondrial toxicity. It has become a ubiquitous term in HIV medicine today. Instead of eradication, it has become more realistic to consider the lifelong management of HIV infection as a chronic...

Complications And Prognosis

Glucocorticosteroid treatment-related adverse events occur commonly among these elderly patients, and at least 65 of patients may have at least one adverse event (3). Patients are at a risk for diabetes mellitus and osteoporosis with osteoporotic fractures, which occur in this patient group at a rate two to five times higher than in age-matched controls. Complications are more frequent in patients over the age of 75 and patients receiving higher doses of steroids (3). All patients should receive calcium and vitamin D supplementation and appropriate treatment for osteoporosis including bisphosphonates.

Acculturation And Psychological Adjustment

Ture plays a role in both the base rate of the necessary condition as well as the base rate of the sufficient condition. Diabetes mellitus, found to have a higher prevalence in some minority groups (e.g., Mexican Americans in South Texas), is another example of how culture plays a role in terms of both the necessary and the sufficient conditions of this illness. Physical illnesses have definite social and psychological impacts on the person afflicted, but also on the person's family, relatives, friends, co-workers, and the like.

Treatment of acute DVT

The duration of anti-coagulant therapy is influenced by balancing the risks of recurrence of thrombosis and of anti-coagulant related haemorrhage (ARH), and by the patient preference. The risk of bleeding during the initial period of anti-coagulation with UFH or LMWHs is 2 to 5 , while the estimated risk of major bleeding with oral anti-coagulant therapy is about 3 annually.156 As 20 of major bleeds are fatal, the annual case fatality rate from ARH is about 0.6 . The risk of bleeding is increased by patient-specific factors, such as, age (65 years or older) and co-morbidity (renal failure, liver disease, diabetes, peptic ulcer disease, cerebrovascular disease, malignancy) and by the concomitant use of anti-platelet agents.157,158 Evidence also indicates that the risk of bleeding on anti-coagulant therapy is reduced over time, so the long-term fatality rate is likely to be lower in patients who have tolerated months or years of anti-coagulant treatment without bleeding. On the other...

Animal Evaluations of MK0677

In additional dog studies, compound 44 (L-163,191) was active (a fourfold increase of peak GH over baseline) orally at 0.0675 mg kg (1 2 responded), at 0.125 mg kg (6 8 responded) and at 0.25 mg kg (7 8 responded). Following intravenous administration 4 4 dogs responded at the 0.025 mg kg level. In a balanced crossover study using eight beagles, compound 44 given orally increased peak GH concentrations in a dose responsive manner with a 5.3-fold increase at 0.25 mg kg, a 9.0-fold increase at 0.50 mg kg, and a 15.8-fold increase at 1.0 mg kg. After a single oral 1 mg kg dose in three dogs, GH levels remained elevated out to 360 min and insulin-like growth factor (IGF-1) was significantly elevated 30 at 480 min (59). The selectivity of L-163,191 (44) had been demonstrated earlier in over 50 in vitro assays in which its IC50 values exceeded 10 M. These included receptors for ligands known to affect GH release such as acetyl choline, galanin, somatostatin, met-enkepha-lin, and clonidene...

Overview Of Racialethic Minority Health

Despite the fact that whites are the older group among the American population, blacks exhibit a 32 higher age-adjusted all-cause mortality rate, when compared to whites. American Indians or Alaska Natives, latinos and Asians or Pacific Islanders exhibit lower age-adjusted all-cause mortality rates by at least 28 than whites (Freid, et al., 2003). A similar scenario can be observed for selected causes of deaths such as heart disease, cancer and diabetes (Table 1). Blacks exhibit 28 and 26 higher age-adjusted mortality rates for disease of the heart and cancer,

Congestive Heart Failure

Past Medical History Past episodes of heart failure hypertension, excess salt or fluid intake noncompliance with diuretics, digoxin, antihypertensives alcoholism, drug use, diabetes, coronary artery disease, myocardial infarction, heart murmur, arrhythmias. Thyroid disease, anemia, pulmonary disease. Cardiac Risk Factors Smoking, diabetes, family history of coronary artery disease or heart failure, hypercholesterolemia, hypertension.

John M Rosenfeld Hungying Kao Ronald M Evans

Endogenous steroid and vitamin hormones as a result of genetic mutation of the receptor or other proteins that function upstream in the regulation of hormone production or function. Furthermore, modulation of receptor function in certain physiological or pathophysiological states is often clinically beneficial. For these reasons, pharmacological administration of natural or synthetic ligands for several receptors is effective in a variety of clinical syndromes, including diseases associated with reproduction and fertility, immune function, obesity, diabetes, heart disease, and cancer. Identification of natural, endogenous ligands and design of synthetic ligands for nuclear receptors is therefore an important area of research not only for understanding the physiology of NRs, but also for pharmacological intervention in a number of medical syndromes.

Neuroprotection By Pparg Activation Against Ab Toxicity

PPARy participates in differentiation, insulin sensitivity, type 2 diabetes, arteriosclerosis, and cancer 67,68 . In particular, PPARy is a critical regulator of adipocyte differentiation 67 , a process also dependent on the Wnt signaling pathway 69 . Recent studies suggest that treatment of insulin resistance with a PPARy agonist retards the development of AD 73 , and recent studies have shown that some anti-inflammatory drugs that are PPARy agonists have neuroprotective actions in different animal models of neurodegeneration 74,75 . Accordingly anti-diabetic thiazolidinedione drugs have been shown to have a potent insulin-sensitizing action 76 that might be mediated through PPARy-mediated inhibition of GSK-3p 77 .

Minority Elderly Data Inadequacies

That may affect the health or the delivery of health care of the minority elderly (e.g., the relationship of obesity to diabetes, the effects of inner-city population density and crime on restrictions in the activities of daily living, or out-of-pocket expenses for the elderly poor).

Cardiovascular Disease

Despite a major decline in mortality by more than 50 in the second half of the 20th century, coronary heart disease (CHD) remains the single largest killer, accounting for 20 of all deaths in developed countries such as the United States, where mean age of manifestation of a first heart attack is 65-70 years (American Heart Association, 2005). The major risk factors for CHD, which include hypertension, hyperlipidemia, smoking and diabetes, are well established, and 80-90 of all CHD patients have prior exposure to at least one of these risk factors (Khot et al., 2003). In the United States, about 700,000 patients have a new heart attack each year. In recent years, the proportion of affected people surviving the acute stage of a heart attack has substantially increased, but the survivors have a risk of another heart attack, stroke and heart failure that is substantially higher than that of the general population (Hurst, 2002). Although there is evidence that much of the subsequent...

The Real World of Health Policy

WHEREAS The term dioxin refers to a group of chemicals that includes furans and biphenyl compounds (the most well-known dioxin being 2,3.7.8-TCDD), and dioxin is a potent human carcinogen and an endocrine-disrupting chemical affecting thyroid and steroid hormones, scientifically linked to endometriosis, immune system impairment, diabetes, neurotoxicity, birth defects, testicular atrophy and reproductive dysfunction and

Carbohydrate Structure and Diversity

The targeting of lysosomal enzymes is also dependent on receptor-mediated endocytosis. In this case, the cation-dependent mannose 6-phosphate receptor (CD-MPR) and the insulin-like growth factor II cation-independent man-nose 6-phosphate receptor (IGF-II CI-MPR) specifically recognize the mannose-6-phosphate moiety on acid hydro-lases destined for lysosomes 34 . Again, multivalency is important CD-MPR binds mannose 6-phosphate with a dissociation constant in the micromolar concentration range, while the dimeric receptor binds tetrameric P-glucuronidase with nanomolar affinity. Both dimeric and tetrameric forms of the receptor are found in the Golgi membrane, and, based on the crystal structure of the dimeric CD-MPR, a model for its high-affinity interaction with P-glucuronidase has been proposed 35 . The IGF-II CI-MPR receptor contains two canonical CRDs presumably capable of promoting high-affinity interactions with multivalent lysosomal enzymes, and together with CD-MPR these...

Health Policies and Human Behavior and Biology

As Rene Dubos (1959, 110) observed decades ago, To ward off disease or recover health, men as well as women and children as a rule find it easier to depend on the healers than to attempt the more difficult task of living wisely. The price of this attitude is partially reflected in the causes of death in the United States. Ranked from highest to lowest by the Centers for Disease Control and Prevention (CDC 2005), the ten leading causes are heart disease, cancer, stroke, chronic lower respiratory diseases, accidents, diabetes, pneumonia influenza, Alzheimer's disease, nephritis nephritic syn-drome nephrosis, and septicemia.

Biomedical Importance

Water is the predominant chemical component of living organisms. Its unique physical properties, which include the ability to solvate a wide range of organic and inorganic molecules, derive from water's dipolar structure and exceptional capacity for forming hydrogen bonds. The manner in which water interacts with a sol-vated biomolecule influences the structure of each. An excellent nucleophile, water is a reactant or product in many metabolic reactions. Water has a slight propensity to dissociate into hydroxide ions and protons. The acidity of aqueous solutions is generally reported using the logarithmic pH scale. Bicarbonate and other buffers normally maintain the pH of extracellular fluid between 7.35 and 7.45. Suspected disturbances of acid-base balance are verified by measuring the pH of arterial blood and the CO2 content of venous blood. Causes of acidosis (blood pH < 7.35) include diabetic ketosis and lactic acidosis. Alkalosis (pH > 7.45) may, for example, follow vomiting...

Isolated Pericardial Hemodynamic Effects And Transplantation

Late toxic metal ions and free calcium concentration titration insulin (10 U L) to aid in glucose utilization sodium pyruvate (2.27 mmol L) as an additional energy substrate and mannitol (16.0 mmol L) to increase osmolarity and reduce cardiac edema. The in vitro approach was employed because, in vivo, ventricular output is coupled to the pulmonary system and flows through the coronary vessels, limiting chamber ejection rates (i.e., right ventricle output cannot be steadily greater than left atrial output). Decoupling these flows in vitro allowed intrinsic output of the left and right side to operate independently with controlled atrial preload.

Lipidlowering Activity

Depression is often associated with insulin resistance, owing to Cortisol overproduction (McCarty 1994). The reputed antidepressant effects of chromium may be explained by improvements in insulin sensitivity (Davidson et al 2003) and related increases in tryptophan availability and or noradrenaline release (McLeod & Golden 2000). Chromium has also been shown to lower the Cortisol response to challenge with 5-hydroxy-L-tryptophan (5-HTP) and decrease the sensitivity of 5-HT2A receptors (Attenburrow et al 2002).

Bone Density Protection

It has been suggested that modulation of Insulin by chromium may have positive effects on bone density, reducing bone resorption and promoting collagen production by osteoblasts (McCarty 1995). One placebo-controlled study using chromium picolinate (equivalent to 200 fjg chromium day for 60 days) has shown a 47 reduction in the urinary hydroxyproline creatinine ratio, indicating a decrease in calcium excretion and a potential role in the prevention of osteoporosis (Evans et al 1995).

Role Of Gsk3 In Neuronal Morphogenesis

Figure 3.2 Some pathways that modulate the kinase activity of GSK-3. These pathways may be classified in two main groups. First are the pathways that act through the inhibition of GSK-3 by increasing Ser9 21 phosphorylatio, such as those triggered by Insulin IGF-1 (IGF1) or by some growth factors (GFs) or by estrogen (E2). However, so far it is still not clear how GSK-3 is inhibited by the action of Wnt in these Wnt pathways. Second are the class of pathways in which GSK-3 is activated by LPA or Reelin. In these systems the precise molecular mechanism of how GSK-3 is activated still has to be defined. See color plates. Figure 3.2 Some pathways that modulate the kinase activity of GSK-3. These pathways may be classified in two main groups. First are the pathways that act through the inhibition of GSK-3 by increasing Ser9 21 phosphorylatio, such as those triggered by Insulin IGF-1 (IGF1) or by some growth factors (GFs) or by estrogen (E2). However, so far it is still not clear how GSK-3...

Treatment Providers

The topic of cultural competence, i.e., ''the ability of a system, agency, or professional to work effectively in cross cultural situations'' (83), has become prominent in the health care literature as the challenge of delivering effective health care to an increasingly diverse population has emerged (11,83,93-95). Unlike the terms''compliance and ''adherence,'' which emphasize client variables as potential barriers to the success of treat-ment,''cultural competence puts the focus on what the provider brings to the treatment relationship and requires self-reflection among health professionals. Providers vary in age (e.g., reflecting both generation effects and life stage), ethnicity, regional background, disciplines, language skills, and gender. There are also wide variations in socioeconomic status, political opinions, values, moral codes, and world views among health professionals. These culturally influenced attributes are not eliminated by professional training, and they influence...

How Is Gsk3 Activity Controlled

Many kinases are involved in the serine phosphorylation of GSK-3, including Akt, ILK, PKA, and p90Rsk. Furthermore the inhibition of GSK-3 has been correlated with serine phosphorylation in many physiological situations, such as stimulation of the Insulin IGF1, NGF, and Estradiol pathways 23 . However, there are fewer candidates that might be responsible for tyrosine phosphorylation of GSK-3. In neurons, the Pyk-2 and fyn kinases are capable of phosphorylating GSK-3 on tyrosine in vitro 24,25 , and more recently MEK1 2 has been shown to fulfill this role in fibroblasts. Furthermore in Dictyostelium there is compelling evidence that ZAK1 is responsible for the tyrosine phosphorylation of GSK-3 26 .

What Should Be Clarified Beforehand

Every patient must be thoroughly questioned and examined with regard to possible concurrent illnesses before starting treatment. These must be considered when choosing a regimen. ddI is contraindicated in patients with pancreatitis. Similarly, pre-existing polyneuropathy requires that any d-drugs (ddI, ddC, d4T) be avoided. Non-insulin-dependent diabetes can become insulin-dependent on PI treatment. In such cases, the use of PIs for first-line therapy should be carefully considered. Liver disease and chronic hepatitis must also be taken into account, because the risk of developing severe hepatotoxicity on nevirapine or ritonavir is highest in these patients (Den Brinker 2000, Martinez 2001, Saves 1999, Sulkowski 2000+2002). However, a recently published study conducted in over 1,000 patients found no difference between lopinavir ritonavir and nelfinavir in patients with hepatitis C (Sulkowski 2004). 3TC or FTC and preferably also tenofovir should be incorporated into the first regimen...

Pathways Controlling Gsk3 Activity In Neurons

Since many different pathways have been described in which GSK-3 plays an important or essential role, we will only summarize some of these here. Historically GSK-3 fulfills a significant role in the Insulin IGF1 and Wnt Shaggy signaling pathways. However, more recently it has become clear that GSK-3 is present in many other pathways such as those involving NGF, Estradiol, or Reelin. Moreover it seems likely that there will be many more in which the 3.5.1 Insulin IGF1 The Insulin IGFl system has been widely studied in neuronal and nonneuronal cells 4 as it is a pathway that controls processes such as survival apoptosis. In this pathway the inhibition of at least one pool of GSK-3 is essential for the survival of certain types of neuron. Furthermore it has been established that the PKB Akt kinase exerts a negative influence on GSK-3 activity in this pathway through serine phosphorylation 21 . The serine phosphorylation of GSK-3 by ILK has also been established as an alternative...

Glycosylated Hemoglobin HbA1c

When blood glucose enters the erythrocytes it glycosylates the e-amino group of lysine residues and the amino terminals of hemoglobin. The fraction of hemoglobin glycosylated, normally about 5 , is proportionate to blood glucose concentration. Since the half-life of an erythrocyte is typically 60 days, the level of glycosylated hemoglobin (HbA1c) reflects the mean blood glucose concentration over the preceding 6-8 weeks. Measurement of HbA1c therefore provides valuable information for management of diabetes mellitus.

Significance Of Gsk3 Activation

It has generally believed that GSK-3 activity is only negatively regulated and that this occurs through the insulin and Wnt pathways. However, its has recently been shown that GSK-3 can also be activated in response to some extracellular stimuli 24,39,49 . Direct measurements of GSK-3 activity in control and LPA-treated neurons, confirmed that GSK-3 activity increases during LPA-induced neurite retraction 46 . Furthermore we more recently found that Reelin and Netrin augmented GSK-3 activity 39,47 . Thus GSK-3 activation by LPA, Netrin, or Reelin seems not to be a particular characteristic of the cell line used but rather a more general physiological process. Indeed, even in situations where the final balance is an inhibition of GSK-3 kinase activity, such as following the addition of IGFl Insulin or after estradiol addition, a transient activation of GSK-3 could be observed 24,37 . All these data suggest that the upregulation and downregulation of this kinase is more complex than...

Uptake of HSPS into Cells

Decreased HSP levels in some tissues have detrimental consequences, and uptake of extracellular HSP may be a mechanism whereby cells with low expression can obtain HSP required for survival. Type 1 diabetes patients with polyneuropathy have very low levels of Hsp72 in blood leucocytes (Strokov et al., 2000). Administration of the anti-oxidant a-lipoic acid, which improves nerve conductance and blood supply to nervous tissue, increased Hsp72 leukocyte levels in these patients accompanied by improvement in nerve damage (Strokov et al., 2000). Uptake of extracellular HSP may have positive effects on other cells with low HSP.

Receptor Subtypes As Novel Targets

The a2-adrenoceptors mediate a number of physiological and pharmacological responses such as hypotension, sedation, inhibition of insulin release, inhibition of lipolysis, and platelet aggregation.5 In contrast to the Gs-coupled p-adrenoceptors and the Gq-coupled a1-adrenoceptors, the a2-adrenoceptors preferentially couple to the Gi Go family of heterotrimeric guanine nucleotide binding proteins and

Lifethreatening Disorders

The 10 leading causes ofdeath in the United States in 1995 were, in order, diseases of heart, malignant neoplasms, cerebrovascular diseases, chronic obstructive pulmonary diseases, accidents and adverse effects, pneumonia and influenza, diabetes mellitus, HIV infection, suicide, and chronic liver disease and cirrhosis (Rosenberg, Ventura, Maurer, Heuser, & Freedman,

Cardiovascular Effects

EGb 761 at a dose of 200 mg administered to 60 patients intravenously for 4 days improved skin perfusion and decreased blood viscosity without affecting plasma viscosity (19). Another GB extract, LI 1730, increased blood flow in nailfold capillaries and decreased erythrocyte aggregation compared to placebo in 10 volunteers at a dose of 112.5 mg (26). Blood pressure, heart rate, packed cell volume, and plasma viscosity were unchanged. A study in subjects with type 2 diabetes mellitus complicated with retinopathy evaluated the effects of administration of GB (EGb 761) for 3 months on erythrocyte hemorrheology (27). At the end of the treatment period, it was observed that blood viscosity was significantly reduced, fibrinogen levels were decreased, and erythrocytes were more deformable. Finally, retinal capillary blood flow was improved. However, in a double-blind, placebo-controlled trial of GB in the treatment of Raynaud's disease, after 10 weeks of treatment there was no improvement in...

Utility Of The System

Phase contrast photomicrographs of normal human articular chondrocytes cultured in (A) serum-containing DMEM FBS or serum-free DRF medium supplemented with (B) insulin, transferrin, and selenium (ITS+) (C) ITS+ and insulin-like growth factor-1 (IGF-1) (D) ITS+, IGF-1, and basic fibroblast growth factor (bFGF) (E) ITS+, IGF, bFGF, and fibronectin (FN) or (F) ITS+, IGF, bFGF, FN, and hydrocortisone (HC). Figure 5. Phase contrast photomicrographs of normal human articular chondrocytes cultured in (A) serum-containing DMEM FBS or serum-free DRF medium supplemented with (B) insulin, transferrin, and selenium (ITS+) (C) ITS+ and insulin-like growth factor-1 (IGF-1) (D) ITS+, IGF-1, and basic fibroblast growth factor (bFGF) (E) ITS+, IGF, bFGF, and fibronectin (FN) or (F) ITS+, IGF, bFGF, FN, and hydrocortisone (HC). Chondrocytes produce and secrete factors that promote their own attachment and proliferation 24 . Examples include bFGF 14 , insulin-like growth factors 13 ,...

Examine the eyes with an ophthalmoscope

The ophthalmoscopic examination of the eye is a vital part of the complete physical examination. It can reveal the effects of systemic conditions such as hypertension and diabetes mellitus, causes of visual dysfunction such as optic atrophy, and reveal conditions such as raised intra-cranial pressure by demonstrating papilloedema. The ocular complications of conditions such as diabetes mellitus may be asymptomatic until sight-threatening complications have developed hence the importance of screening examinations.

Phosphorylation Sites Of Gsk30

The kinase fold of GSK-3P superimposes well on the structures of MAP kinases p38 and ERK2 and also CDK2. The catalytic activity of these kinases depends on the correct alignment of the N- and C-terminal domains, which is usually modulated by two phosphorylated residues in the activation loop. One of the phosphorylated residues (typically a phospho-threonine) binds positively charged residues from the N-terminal and C-terminal domains via its phosphate group. Phosphorylation of the second residue (typically a phospho-tyrosine) opens up the substrate-binding groove. GSK-3P has two phosphorylation sites that regulate the catalytic activity, Ser9 and Tyr216. AKT phosphorylates GSK-3P at Ser9 attenuating enzyme activity. This mechanism of inactivation by phosphorylation is specific for the insulin signaling pathway and is not used in the Wnt signaling pathway 8,9 . GSK-3P has only one phosphorylation site in the activation loop, Tyr216, as opposed to two in MAP kinases. A valine (Val214)...

Using Restriction Enzymes and Plasmids to Clone a Gene

We will use the example of the insulin gene to explain how gene cloning works (figure 5.3). Insulin was the first protein to have its amino acid sequence deciphered. This is because it is relatively small (see table 4.1). It is also one that is very important medically. Figure 5.3.A shows a part of the amino acid sequence of human insulin. Because we know the genetic code if we know the sequence of amino acids of a protein, we can make a sequence of DNA, a gene, that corresponds to the sequence of amino acids in that protein. Figure 5.3.B shows the sequence of DNA corresponding to the amino acid sequence shown in figure 5.3.A. Because many amino acids can be coded for by a number of different codons, the DNA sequence shown is one of many that corresponds to the amino acid sequence. The gene coding for insulin was synthesized in this way in the laboratory. In order to have this gene transcribed at a high level in bacteria, a promoter and terminator are added to the beginning and end of...

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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