Pfeifer M A, Halter J B, Porte D
Am J Med. 1981 Mar;70(3):579-88. doi: 10.1016/0002-9343(81)90579-9.
A brief review of the normal physiology of insulin secretion is given. The dual role of glucose to directly stimulate insulin release and to potentiate insulin secretion to other islet regulators is emphasized. The B cell of the pancreatic islet is discussed as a metabolic integrator for nutrients, modulated by neural and hormonal input. A feedback model for the normal regulation of glucose concentrations is also described. This model is based on a closed loop between the islet, the liver and peripheral tissues for the production and utilization of glucose. Diabetes mellitus with overt hyperglycemia is characterized by impaired pancreatic B-cell function; however, in noninsulin-dependent diabetic subjects, many aspects of insulin secretion are maintained by a compensatory increase in plasma glucose concentration. The model shows why this increase in plasma glucose occurs and the importance of this hyperglycemia to the restoration of insulin responses to nonglucose secretagogues, second-phase insulin secretion to glucose and basal insulin. The model can account for the usual stability of plasma glucose in noninsulin-dependent diabetes mellitus and the very high glucose levels and lack of glucose stability in insulin-dependent diabetes mellitus. Sulfonylurea drugs increase insulin secretion, but this increase is dependent on the glucose level. Thus, the augmented B-cell function can be masked by a decrease in plasma glucose concentrations. During long-term therapy, the insulin level and responses are unchanged despite lower concentrations of glucose. Therefore, it is hypothesized that sulfonylureas still act by enhancement of B-cell function.
本文简要回顾了胰岛素分泌的正常生理学。强调了葡萄糖在直接刺激胰岛素释放以及增强胰岛素对其他胰岛调节因子分泌方面的双重作用。讨论了胰岛β细胞作为营养物质的代谢整合器，受神经和激素输入的调节。还描述了正常血糖浓度调节的反馈模型。该模型基于胰岛、肝脏和外周组织之间关于葡萄糖产生和利用的闭环。明显高血糖的糖尿病以胰腺β细胞功能受损为特征；然而，在非胰岛素依赖型糖尿病患者中，胰岛素分泌的许多方面通过血浆葡萄糖浓度的代偿性增加得以维持。该模型显示了血浆葡萄糖升高的原因以及这种高血糖对于恢复胰岛素对非葡萄糖促分泌剂的反应、葡萄糖的第二相胰岛素分泌和基础胰岛素的重要性。该模型可以解释非胰岛素依赖型糖尿病中血浆葡萄糖通常的稳定性以及胰岛素依赖型糖尿病中非常高的血糖水平和缺乏葡萄糖稳定性的现象。磺脲类药物可增加胰岛素分泌，但这种增加取决于葡萄糖水平。因此，增强的β细胞功能可能被血浆葡萄糖浓度的降低所掩盖。在长期治疗期间，尽管葡萄糖浓度较低，但胰岛素水平和反应不变。因此，推测磺脲类药物仍通过增强β细胞功能发挥作用。
