Polonsky K S, Sturis J, Van Cauter E
Department of Medicine, University of Chicago, Pritzker School of Medicine, Ill 60637, USA.
Horm Res. 1998;49(3-4):178-84. doi: 10.1159/000023168.
In this article, recent experiments are reviewed which have addressed the role of oscillatory insulin secretion in the pathophysiology of glucose intolerance and diabetes. The ultradian oscillations of insulin secretion appear to be an integral part of the feedback loop between glucose and insulin secretion and as a result are abnormal in states of glucose intolerance. Treatment of impaired glucose tolerance with troglitazone, a thiazolidinedione that improves insulin sensitivity, leads to an improvement in the ability of the beta-cell to sense and respond to a glucose stimulus restoring the ability of glucose to entrain the ultradian oscillations. The rapid oscillations of insulin secretion appear to be an inherent feature of the cellular mechanisms of insulin secretion since they persist in the isolated perfused pancreas and in perifused islets. These oscillations are paralleled by changes in intracellular Ca2+ and are also abnormal in states of glucose intolerance and diabetes. Available evidence indicates that these alterations are due to decreased expression of voltage-dependent Ca2+ channels on the beta-cell membrane.
在本文中，我们回顾了近期的实验，这些实验探讨了振荡性胰岛素分泌在葡萄糖不耐受和糖尿病病理生理学中的作用。胰岛素分泌的超日振荡似乎是葡萄糖与胰岛素分泌之间反馈回路的一个组成部分，因此在葡萄糖不耐受状态下是异常的。用曲格列酮治疗糖耐量受损，曲格列酮是一种改善胰岛素敏感性的噻唑烷二酮类药物，可提高β细胞感知和响应葡萄糖刺激的能力，恢复葡萄糖带动超日振荡的能力。胰岛素分泌的快速振荡似乎是胰岛素分泌细胞机制的一个固有特征，因为它们在离体灌注胰腺和周围灌注胰岛中持续存在。这些振荡与细胞内Ca2+的变化平行，在葡萄糖不耐受和糖尿病状态下也是异常的。现有证据表明，这些改变是由于β细胞膜上电压依赖性Ca2+通道的表达减少所致。
