Clinical Aspects

Halki Diabetes Remedy

Alternative Ways to Treat Diabetes

Get Instant Access

A. Peptic Ulcer Disease

The term peptic ulcer refers to an open sore on the esophagus, stomach, or duodenum. The reason why peptic ulcers develop is not well understood. It has been postulated that there is a shift in the balance of mucosa-protecting (secretion of HC03" and mucus) and mucosa-damaging (secretion of acid and pepsin) mechanisms. Peptic ulcer disease can account for as many as 4,000,000 hospital days per year in the United States. Although individuals with duodenal ulcer disease clearly have increased rates of gastric acid secretion, and although gastrin is a potent secretagogue of HC1 secretion, it has not been possible to directly implicate gastrin in the etiology of duodenal ulcer disease.

The drugs cimetidine and ranitidine have a proven value in the treatment of duodenal ulcer disease through their capacity to inhibit the secretion of gastric acid in hypersecretory states, particularly those involving peptic ulceration.

B. Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome is characterized by an advanced ulcer disease of the upper gastrointestinal tract, hypersecretion of gastric acid, and tumors of the pancreas islets. If is estimated that ~1% of operative cases of peptic ulcer disease are individuals with Zollinger-Ellison syndrome. The syndrome results from the release of large quantities of gastrin by the pancreatic islet tumors, probably D cells. This then results in increased secretion of HC1 by the parietal cells of the stomach.

C. Carcinoid Syndrome

The term carcinoid or argentaffinosis is employed to describe a group of intestinal tumors that grow more slowly than the more common intestinal carcinoma. The carcinoid tumor is derived from the enterochro-maffin cells, which are cytochemically indistinguishable from many of the gastrointestinal hormone-secreting cells of the intestinal tract. The most frequent sites of their location are the ileum and the appendix. The chief clinical signs of carcinoid syndrome are flushing and diarrhea.

The chief biochemical lesion is an elevated production of 5-hydroxytryptamine, which results from the conversion of tryptophan to 5-hydroxytryptophan followed by decarboxylation to yield 5-hydroxytrypta-mine. Elevated blood levels of 5-hydroxytryptamine and an increased urinary excretion of 5-hydroxyindole-acetic acid are often diagnostic of the carcinoid syndrome. Also, the tumor contains the enzyme kallikrein (see Chapter 15), which leads to increased plasma levels of bradykinin.

Both pharmacological and surgical treatments are employed to treat carcinoid syndrome.


A. Books

Rang, H. P., Dale, M. M., Ritter, J. M., and Gardner, P. (1995). "Pharmacology," 3rd ed., pp. 1-855. Churchill Livingstone, New York.

B. Review Articles

Blundell, J. (1991). Pharmacological approaches to appetite suppression. Trends Pharmacol. Sci. 12, 147-157. Green, G. M. (1994). Feedback inhibition of cholecystokinin secretion by bile acids and pancreatic proteases. Ann. NY Acad. Sci. 713, 167-179.

Kreil, G., and Wechselberger, C. (1994). Peptides related to cholecys-tokinin in nonmammalian vertebrates. Ann. NY Acad. Sci. 713, 32-38.

Pandol, S. J., Gukovskaya, A., Bahnson, T. D., and Dionne, V. E.

(1994). Cellular mechanisms mediating agonist-stimulated calcium influx in the pancreatic acinar cell. Ann. NY Acad. Sci. 713, 41-48.

Reeve, J. R., Jr., Eysselein, V. E., Ho, F. J., Chew, P., Vigna, S. R., Liddle, R. A., and Evans, C. (1994). Natural and Synthetic CCK-58. Novel reagents for studying cholecystokinin physiology. Ann. NY Acad. Sci. 713, 11-21.

C. Research Papers

Black, J. W., and Shankley, N. P. (1987). How does gastrin act to stimulate oxyntic cell secretion? Trends Pharmacol. Sci. 8,486-489.

DeGiorgio, R., Sternini, C., Anderson, K., Brecha, N. C., and Go, V. L. W. (1992). Tissue distribution and innervation pattern of peptide immunoreactivities in the rat pancreas. Peptides 13,91-98.

DelValle, J., and Yamada, T. (1990). The gut as an endocrine organ. Annu. Rev. Med. 41, 447-455.

Dourish, C. T., Rycroft, W., and Iversen, S. D. (1989). Postponement of satiety by blockade of brain cholecystokinin (CCK-B) receptors. Science 245, 1509-1511.

Drewe, J., Gadient, A., Rovati, L. C., and Beglinger, C. (1992). Role of circulating cholecystokinin in control of fat-induced inhibition of food intake in humans. Gastroenterology 102, 1654-1659.

Edmondson, S., Khan, N., Shriver, J., Zdunek, J., and Graslund, A.

(1991). The solution structure of motilin from NMR distance constraints, distance geometry, molecular dynamics, and an iterative full relaxation matrix refinement. Biochemistry 30, 1127111279.

Evers, B. M., Izukura, M., Chung, D. H., Parekh, D., Yoshinaga, K., Greeley, G. H., Jr., Uchida, T., Townsend, C. M., Jr., and Thompson, J. C. (1992). Neurotensin stimulates growth of colonic mucosa in young and aged rats. Gastroenterology 103, 86-91.

Eysselein, V. E. (1992). Regulation of gastric acid secretion by gastrin in duodenal ulcer patients and healthy subjects. Gastroenterology 102, 1142-1148.

Fatatis, A., Holtzclaw, L. A., Avidor, R., Brenneman, D. E., and Russell, J. T. (1994). Vasoactive intestinal peptide increases intracellular calcium in astroglia: synergism with «-adrenergic receptors. Proc. Natl. Acad. Sci. USA 91, 2036-2040.

Fried, M., Erlacher, U., Schwizer, W., Lochner, C., Koerfer, J., Beglinger, C., Jansen, J. B., Lamers, C., Harder, F., Bischof-Delaloye, A., Stalder, A., and Rovati, L. (1991). Role of cholecystokinin in the regulation of gastric emptying and pancreatic enzyme secretion in humans. Studies with the cholecystokinin receptor antagonist loxiglumide. Gastroenterology 101, 503-511.

Hearn, S. C., Jones, P. M., Ghatei, M. A., Byrne, J., Hill, S. F„ and Bloom, S. R. (1992). The presence, characterization and synthesis of neuromedin B in the human pituitary gland. Neuroendocrinol-ogy 56, 729-735.

Ishihara, T., Shigemoto, R., Mori, K., Takahashi, K., and Nagata, S.

(1992). Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide. Neuron 8, 811819.

Ishihara, T., Nakamura, S., Kaziro, Y., Takahashi, T., Takahashi, K., and Nagata, S. (1991). Molecular cloning and expression of a cDNA encoding the secretin receptor. EMBO J. 10, 1635-1641.

Jaffe, B. M. (1992). Current issues in the management of ZollingerEllison syndrome. Surgery 111, 241-250.

Jia, X., Brown, J. C„ Ma, P., Pederson, R. A., and Mcintosh, C. H. S.

(1995). Effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-I-(7-36) on insulin secretion. Am. ]. Physiol. (Endocrin. Metab. 31) 268, E645-E651.

Jiang, S., and Ulrich, C. (1995). Molecular cloning and functional expression of a human pancreatic secretin receptor. Biochem. Bio-phys. Res. Commun. 207, 883-890.

Kopin, A. S„ Lee, Y. M„ McBride, E. W., Miller, L. J., Lu, M., Lin, H. Y., Kolakowski, L. F., and Beinborn, M. (1992). Expression cloning and characterization of the canine parietal cell gastrin receptor. Proc. Natl. Acad. Sci. USA 89, 3605-3609.

Kopin, A. S., Wheeler, M. B., Nishitani, J., McBride, E. W., Chang, T., Chey, W. Y., and Leiter, A. B. (1991). The secretin gene: Evolutionary history, alternative splicing, and developmental regulation. Proc. Natl. Acad. Sci. USA 88, 5335-5339.

Kopin, A. S., Wheeler, M. B., and Leiter, A. B. (1990). Secretin: Structure of the precursor and tissue distribution of the mRNA. Proc. Natl. Acad. Sci. USA 87, 2299-2303.

Krane, I. M., Naylor, S. L., Helin-Davis, D., Chin, W. W„ and Spindel, E. R. (1988). Molecular cloning of cDNAs encoding the human bombesin-like peptide neuromedin B. J. Biol. Chem. 263, 1331713323.

Kroog, G. S., Sainz, E., Worland, P. J., Akeson, M. A., Benya, R. V., Jensen, R. T., and Battey, J. F. (1995). The gastrin-releasing peptide receptor is rapidly phosphorylated by a kinase other than protein kinase C after exposure to agonist. /. Biol. Chem. 270, 8217-8224.

Lacroix, A., Bolte, E., Tremblay, J., Dupre, J., Poitras, P., Foumier, H., Garon, J., Garrel, D., Bayard, F., Taillefer, R., Flanagan, R. J., and Hamet, P. (1992). Gastric inhibitory polypeptide-dependent Cortisol hypersecretion: a new cause of Cushing's syndrome. New Engl. J. Med. 327, 974-979.

Liddle, R. A. (1994). Regulation of cholecystokinin gene expression in rat intestine. Ann. NY Acad. Sci. 713, 22-31.

Maton, P. N. (1988). The carcinoid syndrome. /. Am. Med. Assoc. 260, 1602-1605.

McKnight, G. L., Karlsen, A. E., Kowalyk, S., Mathewes, S. L., Shep-pard, P. O., O'Hara, P. J., and Taborsky, G. J., Jr. (1992). Sequence of human galanin and its inhibition of glucose-stimulated insulin secretion from RIN cells. Diabetes 41, 82-87.

Miralles, P., Peiero, E., Degano, P., Silvestre, R. A., and Marco, J. (1990). Inhibition of insulin and somatostatin secretion and stimulation of glucagon secretion by homologous galanin in perfused rat pancreas. Diabetes 39, 996-1001.

Nagalla, S. R., Gibson, B. W., Tang, D., Reeve, J. R., and Spindel, E. R. (1992). Gastrin-releasing peptide (GRP) is not mammalian bombesin: identification and molecular cloning of a true amphibian GRP distinct from amphibian bombesin in Bombina orientalis. J. Biol. Chem. 267, 6916-6922.

Niederau, C., Luthen, R„ and Heintges, T. (1994). Effects of CCK on pancreatic function and morphology. Ann. NY Acad. Sci. 713, 180-198.

Rang, H. P., Dale, M. M., Ritter, J. M., and Gardner, P. (1995). The gastrointestinal tract. In "Pharmacology," 3rd ed., Chapter 19, pp. 385-402. Churchill Livingstone, New York.

Rattan, S. (1991). Role of galanin in the gut. Gastroenterology 100, 1762-1768.

Rohner-Jeanrenaud, F., and Jeanrenaud, B. (1996). Obesity, leptin, and the brain. New Engl. ]. Med. 334, 324-325.

Rothstein, R. D., Johnson, E., and Ouyang, A. (1991). Distribution and density of substance P receptors in the feline gastrointestinal tract using autoradiography. Gastroenterology 100, 15761581.

Sandvik, A. K., and Waldum, H. L. (1991). CCK-B (gastrin) receptor regulates gastric histamine release and acid secretion. Am. /. Physiol. 260, G925-G928.

Schjoldager, B. T. G. (1994). Role of CCK in gallbladder function. Ann. NY Acad. Sci. 713, 207-213.

Shriver, J., and Edmondson, S. (1993). Defining the precision with which a protein structure is determined by NMR. Application to motilin. Biochemistry 32, 1610-1617.

Spindel, E. R., Zilberberg, M. Dv and Chin, W. W. (1987). Analysis of the gene and multiple mRNAs encoding human gastrin releasing peptide (GRP): Alternate RNA splicing occurs in neural and endocrine tissue. Mol. Endocrinol. 1, 224-232.

Sreedharan, S. P., Patel, D. R., Xia, M., Ichikawa, S., and Goetzl, E. J. (1994). Human vasoactive intestinal peptide] receptors expressed by stable transfectants couple to two distinct signaling pathways. Biochem. Biophys. Res. Commun. 203, 141-148.

Symes, A., Lewis, S., Corpus, L., Rajan, P., Hyman, S. E., and Fink, J. S. (1994). STAT proteins participate in the regulation of the vasoactive intestinal peptide gene by the ciliary neurotrophic factor family of cytokines. Mol. Endocrinol. 8, 1750-1763.

Tanaka, K., Masu, M., and Nakanishi, S. (1990). Structure and functional expression of the cloned rat neurotensin receptor. Neuron 4, 847-854.

Thor, K., and Rosell, S. (1986). Neurotensin increases colonic motility. Gastroenterology 90, 27-31.

Wada, E„ Way, J., Lebacq-Verhaden, A. M„ and Batley, J. F. (1990). Neuromedin B and gastrin-releasing peptide mRNAs differentially distributed in the rat nervous system. Neuroscience 19,29172930.

Wank, S. A., Harkins, R., Jensen, R., Shapira, H., deWeerth, A., and Slattery, T. (1992a). Purification, molecular cloning, and functional expression of the cholecystokinin receptor from rat pancreas. Proc. Natl. Acad. Sci. USA 89, 3125-3129.

Wank, S. A., Pisegna, J. R., and de Weerth, A. (1992b). Brain and gastrointestinal cholecystokinin receptor family: structure and functional expression. Proc. Natl. Acad. Sci. USA 89, 86918695.

Wilding, J. P. H., Ghatei, M. A., and Bloom, S. R. (1995). Hormones of the gastrointestinal tract. In "Endocrinology" (L. J. DeGroot, M. Besser, H. G. Burger, J. L. Jameson, D. L. Loriaux, J. C. Marshall, W. D. Odell, J. T. Potts, Jr., and A. H. Rubenstein, eds.), 3rd ed., Vol. 3, Chapter 153, pp. 2870-2894. W. B. Saunders Company, Philadelphia, PA.

Wiley, J. W., Lu, Y., and Owyang, C. (1991). Mechanism of action of peptide YY to inhibit gastric motility. Gastroenterology 100, 865-872.

Wolfe, M. M., and Soil, A. H. (1988). The physiology of gastric acid secretion. New Engl. J. Med. 319, 1707-1715.

Yamada, Y., Post, S. R., Wang, K„ Tager, H. S., Bell, G. I., and Seino, S. (1992). Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. Proc. Natl. Acad. Sci. USA 89, 251-255.

Zachary, I., Gil, J., Lehmann, W., Sinnett-Smith, J., and Rozengurt, E. (1991). Bombesin, vasopressin and endothelin rapidly stimulate tyrosine phosphorylation in intact Swiss 3T3 cells. Proc. Natl. Acad. Sci. USA 88, 4577-4581.

Was this article helpful?

0 0
Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook

Post a comment