Inhibition of insulin secretion: a fail-safe system

Insulin secretion from the beta-cells of the endocrine pancreas is subject to a pot-pourri of stimulatory, modulatory and inhibitory influences. beta-Cell secretion is reduced or blocked by a variety of inhibitors (including galanin, somatostatin and noradrenaline) which reach the cells either via the islet vascular system or are released locally from sympathetic and peptidergic nerves terminating in the pancreas. It is now becoming clear that among these many inhibitors, several have multiple mechanisms by which they inhibit release at the cellular level. Indeed, with multiple inhibitors (some of which are co-secreted) and multiple mechanisms of inhibition, the latter including a late effect in stimulus secretion coupling (perhaps on the exocytotic step per se), inhibition of insulin secretion has the characteristics of a fail-safe system.