Cellular loci of sulfonylurea actions.
Sulfonylurea drugs exert their chronic antidiabetic actions through both extrapancreatic and pancreatic effects. The major extrapancreatic effect is a potentiation of insulin action. Evidence exists to suggest that this potentiation of insulin action occurs at a postreceptor site in insulin-sensitive cells; however, it is not possible to exclude absolutely some contributory primary effect on increasing insulin receptor binding. Not all insulin-sensitive tissues and processes are equally affected by sulfonylureas. Acute pancreatic actions of sulfonylureas include stimulation of basal and nutrient-stimulated insulin secretion. Impairment of proinsulin biosynthesis and in some instances inhibition of nutrient-stimulated insulin secretion may follow chronic (greater than several months) administration of sulfonylureas. The acute sulfonylurea-stimulated secretion of insulin is probably the result of sulfonylurea binding to the beta cell plasma membrane followed by alterations in ionic fluxes. Whether the extrapancreatic potentiation of insulin action results from a similar mechanism of action is presently unknown.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D050260:Carbohydrate Metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects*; D011485:Protein Binding; D011972:Receptor, Insulin / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D001798:Blood Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D011972:Receptor, Insulin; D005947:Glucose