Meglasson M D, Nelson J, Nelson D, Erecinska M
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia.
Metabolism. 1989 Dec;38(12):1188-95. doi: 10.1016/0026-0495(89)90158-3.
The relationship of fuel-stimulated insulin secretion and the beta-cell bioenergetic state was investigated in isolated rat islets. In islets perifused with 5 mmol/L glucose to maintain a high basal energy state, stimulation by 9 to 28 mmol/L glucose increased the [ATP]/[ADP] and [GTP]/[GDP]. The rise in the former occurred prior to, or coincident with, the onset of insulin secretion and was dependent on glucose concentration. The increase in the latter appeared to lag behind the alteration in the [ATP]/[ADP] and achieved statistical significance after 30 minutes of incubation. Addition of 20 mmol/L alpha-ketoisocaproic acid, a powerful secretagogue, also caused a rise in the [ATP]/[ADP]. By contrast, 20 mmol/L lactate, which affected insulin secretion only minimally, failed to alter nucleotide concentrations. These data support the hypothesis that an increase in the islet energy state is a metabolic signal linking fuel metabolism with initiation of insulin secretion.
在分离的大鼠胰岛中研究了燃料刺激的胰岛素分泌与β细胞生物能状态之间的关系。在以5 mmol/L葡萄糖进行灌流以维持高基础能量状态的胰岛中，9至28 mmol/L葡萄糖的刺激增加了[ATP]/[ADP]和[GTP]/[GDP]。前者的升高发生在胰岛素分泌开始之前或与之同时，并且依赖于葡萄糖浓度。后者的增加似乎滞后于[ATP]/[ADP]的变化，并且在孵育30分钟后达到统计学显著水平。添加20 mmol/Lα-酮异己酸（一种强效促分泌剂）也导致[ATP]/[ADP]升高。相比之下，20 mmol/L乳酸对胰岛素分泌的影响极小，未能改变核苷酸浓度。这些数据支持以下假设，即胰岛能量状态的增加是一种将燃料代谢与胰岛素分泌起始联系起来的代谢信号。
