Iexocrine Pancreas

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A. The exocrine pancreas consists of acinar cells, which secrete digestive enzymes.

1. The digestive enzymes secreted by acinar cells include trypsinogen, chy-motrypsinogen, procarboxypeptidase, lipase, amylase, elastase, ribonuclease, and deoxyribonuclease.

2. Secretion of digestive enzymes is stimulated by cholecystokinin (CCK) released by I cells of the small intestine (see Chapter 14; II C).

B. The exocrine pancreas contains a network of ducts that delivers digestive enzymes to the duodenum and secretes bicarbonate (HCOy). Secretion of bicarbonate is stimulated by secretin released by S cells of the small intestine (see Chapter 14; II C).

II. ISLETS OF LANGERHANS consist mainly of the following cell types (Figure 17-1).

A. Alpha (a) cells secrete glucagon in response to hypoglycemia to elevate blood glucose, free fatty acid, and ketone levels.

B. Beta (p) cells secrete insulin in response to hyperglycemia to lower blood glucose, free fatty acid, ketone levels.

C. Delta (8) cells secrete somatostatin, which inhibits hormone secretion from nearby cells.

III. INSULIN RECEPTOR AND SIGNAL TRANSDUCTION (Figure 17 2). A receptor (e.g., insulin receptor) that activates a chain of cellular events through the autophos-phorylation of tyrosine is callcd a receptor tyrosine kinase (see Chapter 1; V B).

A. When insulin hinds to the insulin receptor, tyrosine kinase autophosphorylates tyrosine residues within the insulin receptor.

B. The phosphorylated insulin receptor subsequently catalyzes the phosphorylation of insulin receptor substrate-1 (IRS-1).

C. The phosphorylated IRS-1 plays a role in the following:

1. Activation and deactivation of many metabolic enzymes

2. Activation of phosphatidylinositol 3-kinase (PI 3 kinase) to produce inositol 3,4-phosphate and inositol 3,4,5-phosphate, which causes translocation of glucose transporters to the cell membrane

3. Activation of Ras protein, Raf protein kinase, and mitogen-activated protein

GLUCAGON

Liver

INSULIN

1 Glycogen degradation (glycogen phosphorylase)

1 Gluconeogenesis (fructose 1,6 bisphosphatase) (pyruvate kinase)

Adipose t Lipolysis (triacylglycerol lipase) f ^Oxidation of free fatty acids t Lipolysis (triacylglycerol lipase) f ^Oxidation of free fatty acids

Elevates blood glucose, free fatty acids, and ketone levels

Liver t Glucose uptake t Glucose uptake

I Glycogen synthesis (glycogen synthase)

| Glycolysis (phosphofructokinase) (pyruvate dehydrogenase)

t Fatty acid synthesis

Adipose t Glucose uptake | Triacylglyceride synthesis

Skeletal muscle

lucose uptake

| Glycogen synthesis 1 (glycogen synthase)

I Glycolysis (phosphofructokinase) (pyruvate dehydrogenase)

Lowers blood glucose, free fatty acids, and ketone levels

Figure 17-1. The effect of glucagon and insulin on target tissues. The target tissues of glucagon are the liver and adipose. The target tissues of insulin are liver, adipose, and skeletal muscle. The main biochemical pathways and enzymes (in parentheses) that are affected by glucagon and insulin are indicated. The alpha (a) cells (shaded), beta (fi) cells (white) and delta (8) cells (black) are shown with the islet of Langerhans. (Figure of islet: Reprinted with permission from Henrikson RC, Kaye Gl, Mazurkiewicz JE: NMS Histology. Baltimore, Williams and Wilkins, 1997, p 368.)

(Insulin)

(Insulin)

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