Biosynthesis, Secretion, and Metabolism

Somatostatin was originally isolated from hypotha-lamic extracts that inhibited the secretion of growth hormone. Somatostatin is widely distributed in many neural tissues where it presumably functions as a neurotransmitter. It is found in many secretory cells (delta cells) outside of the pancreatic islets, particularly in the lining of the gastrointestinal tract. Somatostatin is stored in membrane-bound vesicles and secreted by exocytosis. Measurable increases in the somatostatin concentration can be found in peripheral blood after ingestion of a meal rich in fat or protein, with the vast majority secreted by intestinal cells rather than islet cells. It is cleared rapidly from the blood and has a halflife of only about 3 min.

Physiologic Actions

The physiologic importance of pancreatic somatos-tatin is not understood. Because it can inhibit secretion of both insulin and glucagon, it has been suggested that somatostatin, by acting in a paracrine fashion, may contribute to the regulation of glucagon and insulin secretion. However, anatomic relationships and the direction of blood flow in the microcirculation in the islets are inconsistent with such a role. Somatostatin also inhibits secretion of various gastrointestinal hormones and decreases acid secretion by the gastric mucosa and enzyme secretion by the acinar portion of the pancreas. In addition, somatostatin decreases intestinal motility and may slow the rate of absorption of nutrients from the digestive tract. Increased fecal excretion of fat is a prominent feature in patients suffering from somatostatin-secreting tumors. At the cellular level the inhibitory effects of somatostatin are mediated by G-protein-coupled receptors that signal through Gai to inhibit adenylyl cyclase, and through y8y-subunits that activate potassium channels and hyperpolarize cell membranes.

Regulation of Secretion

Increased concentrations of glucose or amino acids in blood stimulate somatostatin secretion by intestinal delta cells. In addition, glucose or fat in the gastrointestinal tract elicits a secretory response by pancreatic delta cells, mediated perhaps by glucagon or gastrointestinal hormones. Somatostatin secretion is also increased by norepinephrine and inhibited by acetylcholine.

Suggested Reading

Becker AB, Roth RA. Insulin receptor structure and function in normal and pathological conditions. Ann Rev Med 1990;41:99-116.

Burant CF, Sivitz WI, Fukumoto H, Kayano T, Nagamatsu S, Seino S, Pessin JE, Bell GI. Mammalian glucose transporters: Structure and molecular regulation. Rec Prog Horm Res 1991; 47:349-387.

Cheatham B, Kahn CR. Insulin action and the insulin signaling network. Endocr Rev 1995;16:117-142.

Jefferson LS, Cherrington AD., eds. Handbook of physiology, Section 7, Endocrinology, Vol II. The endocrine pancreas and regulation of metabolism, 2001, New York: Oxford University Press.

(This volume covers a wide range of topics relevant to items discussed in this chapter.)

Kieffer TJ, Habener JF. The glucagon-like peptides. Endocr Rev 1999;20:876-913.

Kimball SR, Vary TC, Jefferson LS. Regulation of protein synthesis by insulin. Ann Rev Physiol 1994;56:321-348.

Miller RE. Pancreatic neuroendocrinology: Peripheral neural mechanisms in the regulation of the islets of Langerhans. Endocr Rev 1981;2:471-494.

Pilkis SJ, Granner DK. Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Ann Rev Physiol 1992;54:885-909.

Rajan AS, Aguilar-Bryan L, Nelson DA, Yaney GC, Hsu WH, Kunze DL, Boyd AE, III. Ion channels and insulin secretion. Diabetes Care 1990;13:340-363.

Taylor SI, Cama A, Accili D, Barbetti F, Quon MJ, de la Luz Sierra M, Suzuki Y, Koller E, Levy-Toledano R, Wertheimer E, Moncada VY, Kadowaki H, Kadowaki T. Mutations in the insulin receptor gene. Endocr Rev 1992;13:566-595. Unger RH, Orci L. Physiology and pathophysiology of glucagon. Physiol Rev 1976;56:778-838.

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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