Insulin secretagogues: old and new

Insulin secretagogues are drugs that increase endogenous insulin secretion. There are three classes of insulin secretagogues: sulfonylureas, meglitini des, and D-phenylalanine derivatives. All stimulate insulin release by clos ing the K-ATP channel of the beta-cell plasma membrane, Differences in thei r pharmacologic action are determined by their pharmacokinetic characterist ics and the affinity and kinetics of their binding to their receptors on th e K-ATP channel. Insulin secretagogues vary, from those that act very rapid ly and have a short duration of action to those that act slow;ly and have a prolonged duration of action, They increase both basal and glucose-stimula ted insulin secretion. The glucose dependence of their insulin secretory ac tion appears to differ somewhat among the various drugs. Insulin secretagog ues can achieve decreases in fasting plasma glucose of 50-80 mg/dl and in H bA(1c) of 1.0-2.5% in most new-ly diagnosed type 2 diabetic patients. Since beta-cell function in type 2 diabetic patients decreases with time, insuli n secretagogues are very effective in reducing hyperglycemia during the fir st few pars of clinically diagnosed diabetes and are relatively ineffective in many people who have had clinically diagnosed type 2 diabetes for >10 y ears. Their major side effects are hypoglycemia and weight gain. The extent to which these side effects occur depends on the characteristics of the ac tion of the specific insulin secretagogue, Cardiovascular tissues also cont ain K-ATP channels, Some insulin secretagogues have significant interaction s with those cardiovascular K-ATP channels and others do not. There are dat a to indicate that the cardiovascular response to ischemia and hypoxia can be altered by some but not all insulin secretagogues.