Insulin, Glucagon and Somatostatin.

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Insulin, Glucagon and Somatostatin

The principal role of the pancreatic hormones is the regulation of whole-body energy metabolism, principally by regulating the concentration and activity of numerous enzymes involved in catabolism and anabolism of the major cell energy supplies.

The earliest of these hormones recognized was insulin, whose major function is to counter the concerted action of a number of hyperglycemia-generating hormones and to maintain low blood glucose levels. Because there are numerous hyperglycemic hormones, untreated disorders associated with insulin generally lead to severe hyperglycemia and shortened life span. Insulin is a member of a family of structurally and functionally similar molecules that include the insulin-like growth factors (IGF-1 and IGF-2), and relaxin. The tertiary structure of all 4 molecules is similar, and all have growth-promoting activities, but the dominant role of insulin is metabolic while the dominant roles of the IGFs and relaxin are in the regulation of cell growth and differentiation.

Insulin is synthesized as a preprohormone in the β cells of the islets of Langerhans. Its signal peptide is removed in the cisternae of the endoplasmic reticulum and it is packaged into secretory vesicles in the Golgi, folded to its native structure, and locked in this conformation by the formation of 2 disulfide bonds. Specific protease activity cleaves the center third of the molecule, which dissociates as C peptide, leaving the amino terminal B peptide disulfide bonded to the carboxy terminal A peptide.

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Insulin secretion from β cells is principally regulated by plasma glucose levels, but the precise mechanism by which the glucose signal is transduced remains unclear. One possibility is that the increased uptake of glucose by pancreatic β-cells leads to a concommitant increase in metabolism. The increase in metabolism leads to an elevation in the ATP/ADP ratio. This in turn leads to an inhibition of an ATP-sensitive K+ channel. The net result is a depolarization of the cell leading to Ca2+ influx and insulin secretion.

Chronic increases in numerous other hormones (including GH, hPL, estrogens, and progestins), up-regulate insulin secretion, probably by increasing ...

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