Regulation of Pancreatic Insulin and Glucagon Secretion

Abstract

Homeostatic regulation of metabolic fuels involves the generally opposing actions of insulin and glucagon. As most agents simultaneously affect secretion of both hormones, this review attempts, when possible, to discuss regulation of insulin and glucagon secretion as related events. The effects of stimulators and inhibitors of insulin and glucagon secretion have been systematically investigated in vivo and in vitro (116,208,244,287, 322). The underlying molecular mechanisms are usually studied by measurement of islet metabolites, cyclic nucleotides, ions, and macromolecules, but holistic interpreta­ tion of these data is complicated by: (a) difficulties in measuring changes with time; (b) the functional significance of cellular compartments; and (c) the limited number of parameters that can be measured simultaneously. These difficulties are com­ pounded for glucagon because normal islets contain 15-30% A cells. Although islets comparatively rich in A cells derived from animals treated with alloxan or streptozotocin have been used to study A-cell secretory biology (31, 186,257), these cells may not be normal, as they have been chronically subjected to a diabetic environment. This problem may be minimized by maintaining such islets in tissue culture-a procedure that retains the high A-cell population and its response to