Endosulfines: Novel regulators of insulin secretion

ATP-dependent potassium (K(ATP)) channels are at a key position in the control of insulin release from pancreatic beta-cells, as they couple the polarity of the cell membrane to the cell metabolism. These channels turn to a closed state when intracellular ATP rises, following an increase in glucose metabolism. These channels are also controlled by sulfonylureas, a class of drugs used in type 2 diabetic patients for triggering insulin secretion. We have obtained evidence of the existence of endogenous equivalents to sulfonylureas in the central nervous system and other K(ATP) channel-containing tissues (including the endocrine pancreas). These molecules, of a peptidic nature, have been called "endosulfines" (for "endogenous sulfonylureas"). In this review, we describe the discovery, isolation and biological features of these molecules--which represent novel regulators of insulin secretion--and the molecular cloning of the large molecular mass form (alpha-endosulfine), and discuss their possible implication in the physiology of beta-cells, as well as in pathology.