丙酮酸循环回补反应与葡萄糖刺激的胰岛素分泌的关系

Role of pyruvate cycling anaplerosis in glucose-stimulated insulin secretion

葡萄糖刺激的胰岛素分泌对维持机体葡萄糖代谢的稳态起着至关重要的作用。在此过程中,β细胞的线粒体一方面利用葡萄糖酵解产生的ATP引起ATP依赖的KATP通道关闭,Ca2+通道开放,Ca2+内流,促进胰岛素囊泡向胞外分泌;另一方面通过KATP通道非依赖途径,利用丙酮酸回补反应使葡萄糖充分酵解,既补充了由于糖酵解循环代谢造成的中间物的流失,又生成了促进胰岛素分泌的中间产物及促使ATP/ADP比率的增加,进一步促进胰岛素的释放。该文对丙酮酸回补反应的3个途径,即丙酮酸-苹果酸循环途径,丙酮酸-柠檬酸循环途径和丙酮酸-异柠檬酸循环途径,及其在胰岛素分泌中的作用等方面的研究进展进行了综述。

Glucose-stimulated insulin secretion （GSIS） is crucial to maintaining normal metabolic glucose homeostasis. Beta cell mitochondria plays a key role in this process, not only by provi- ding energy in the form of ATP, which serves to suppress ATP- sensitive K ＋ （K_ATP） channels and activate voltage-gated Ca2. channels, leading to stimulation of insulin granule exocytosis, but also by synthesizing metabolites （anaplerosis） that can act, both intra- and extra-mitochondrially, as factors that couple glu- cose sensing to insulin granule exocytosis through ATP-sensitive K - （ K_ATP ） channel -independent pathways. More recent studies have demonstrated that the anaplcrotic pyruvate metabolism isimportant in control of insulin secretion, including the pyruvate/malate cycle, the pyruvate/citrate cycle, the pyruvate/isocitrate cycle. These three pathways enable these intermediate（s） to be recycled into and out of mitochondrion, allowing continuous pro- duction of intracellular messenger（s）. The purpose of this review is to present an account of recent progress on the role of each of these pathways in control of insulin secretion.