Bataille D
Institut National de la Sante et de la Recherche Medicale, Montpellier Cedex, France.
Drug News Perspect. 2000 Oct;13(8):453-62.
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.
ATP 依赖性钾通道（K(ATP)通道）在控制胰腺β细胞释放胰岛素的过程中处于关键位置，因为它们将细胞膜的极性与细胞代谢联系起来。当葡萄糖代谢增加导致细胞内 ATP 升高时，这些通道会转变为关闭状态。这些通道也受磺脲类药物的控制，磺脲类药物是用于 2 型糖尿病患者以触发胰岛素分泌的一类药物。我们已经获得证据表明，在中枢神经系统和其他含有 K(ATP)通道的组织（包括内分泌胰腺）中存在磺脲类药物的内源性类似物。这些具有肽性质的分子被称为“内磺素”（意为“内源性磺脲类药物”）。在这篇综述中，我们描述了这些代表胰岛素分泌新调节因子的分子的发现、分离及生物学特性，以及大分子形式（α-内磺素）的分子克隆，并讨论了它们在β细胞生理学以及病理学中的可能作用。
