DIACYLGLYCEROL & C-KINASE AT INTERACELLULAR MEDIATORS

胰岛素调节代谢功能的机制

The mechanisms whereby insulin regulates metabolic functions in target tissues are unknown. In particular, the intracellular signaling system that mediates the insulin effect of glucose transport has not been defined. Many recent findings suggest that the diacylglycerol-C-kinase signaling system could play an important role during insulin-induced increases in glucose transport and other metabolic functions. To summarize these findings: (a) insulin stimulates phospholipid metabolism, diacylglycerol generation and activation of C-kinase; (b) C-kinase activation (by various means) provokes insulin-like effects on glucose transport, amino acid transport and pyruvate dehydrogenase activation; and (c) the glucose transporter is phosphorylated by C-kinase. The present research proposal will study further the hypothesis that the diacylglycerol-C-kinase signaling system serves as an intracellular mediator for insulin effects on glucose transport and other metabolic processes. In particular, we will determine (a) how insulin increases diacylglycerol content; (b) how insulin increases C-kinase activity; (c) target tissues wherein insulin increases diacylglycerol and C- kinase; and (d) the more important consequences of insulin- induced increases in diacylglycerol and C-kinase.