Aspinwall C A, Lakey J R, Kennedy R T
Department of Chemistry, University of Florida, Gainesville, Florida 32611-7200, USA.
J Biol Chem. 1999 Mar 5;274(10):6360-5. doi: 10.1074/jbc.274.10.6360.
Functional insulin receptors are known to occur in pancreatic beta cells; however, except for a positive feedback on insulin synthesis, their physiological effects are unknown. Amperometric measurements at single, primary pancreatic beta cells reveal that application of exogenous insulin in the presence or absence of nonstimulatory concentrations of glucose evokes exocytosis mediated by the beta cell insulin receptor. Insulin also elicits increases in intracellular Ca2+ concentration in beta cells but has minimal effects on membrane potential. Conditions where the insulin receptor is blocked or cell surface concentration of free insulin is reduced during exocytosis diminishes secretion induced by other secretagogues, providing evidence for direct autocrine action of insulin upon secretion from the same cell. These results indicate that the beta cell insulin receptor can mediate positive feedback for insulin secretion. The presence of a positive feedback mechanism for insulin secretion mediated by the insulin receptor provides a potential link between impaired insulin secretion and insulin resistance.
已知功能性胰岛素受体存在于胰腺β细胞中；然而，除了对胰岛素合成的正反馈作用外，其生理效应尚不清楚。对单个原代胰腺β细胞进行的安培测量显示，在存在或不存在非刺激浓度葡萄糖的情况下应用外源性胰岛素，会引发由β细胞胰岛素受体介导的胞吐作用。胰岛素还会引起β细胞内钙离子浓度升高，但对膜电位影响极小。在胞吐作用期间胰岛素受体被阻断或游离胰岛素的细胞表面浓度降低的情况下，其他促分泌剂诱导的分泌会减少，这为胰岛素对同一细胞分泌的直接自分泌作用提供了证据。这些结果表明，β细胞胰岛素受体可介导胰岛素分泌的正反馈。由胰岛素受体介导的胰岛素分泌正反馈机制的存在，为胰岛素分泌受损与胰岛素抵抗之间提供了潜在联系。
