DIACYLGLYCEROL & C-KINASE AT INTERACELLULAR MEDIATORS

二酰甘油

• 批准号: 3237242
• 负责人: ROBERT V FARESE
• 金额: $ 10.26万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1992-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3237242
• 关键词: adipocytes; aminoacid metabolism; calcium binding protein; calcium transporting ATPase; calmodulin; cell growth regulation; chromosome translocation; cyclic AMP; cytoskeleton; diabetes mellitus; diacylglycerols; enzyme mechanism; glucose metabolism; glucose transport; insulin receptor; insulinlike factor; laboratory rat; lipid metabolism; liver cells; molecular pathology; monoclonal antibody; monocyte; peptides; phospholipase C; phospholipids; phosphorylation; protein kinase C; protein tyrosine kinase

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.

胰岛素调节代谢功能的机制 靶组织未知。 特别是细胞内 介导葡萄糖胰岛素作用的信号系统 运输尚未定义。 最近的许多发现表明 二酰基甘油-C-激酶信号系统可以发挥 在胰岛素诱导的葡萄糖增加过程中的重要作用 运输和其他代谢功能。 总结这些 发现：（a）胰岛素刺激磷脂代谢， 二酰基甘油的产生和C-激酶的激活； （b）C-激酶 激活（通过各种方式）促进了胰岛素样影响 葡萄糖转运，氨基酸转运和丙酮酸 脱氢酶激活； （c）葡萄糖转运蛋白是 由C-激酶磷酸化。 本研究建议将 进一步研究二酰基甘油-C-激酶的假设 信号系统用作胰岛素的细胞内介体 对葡萄糖转运和其他代谢过程的影响。 在 特别是，我们将确定（a）胰岛素如何增加 二酰基甘油含量； （b）胰岛素如何增加C-激酶活性； （c）胰岛素增加二酰基甘油和C-的靶组织 激酶； （d）胰岛素 - 更重要的后果 - 诱发的二酰基甘油和C-激酶的增加。