THE INTERPLAY BETWEEN CALCIUM AND CYCLIC AMP IN DIABETES

糖尿病中钙和环磷酰胺之间的相互作用

• 批准号: 3086255
• 负责人: ROCHELLE M HANLEY
• 金额: $ 7.59万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3086255
• 关键词: calcium metabolism; calmodulin; cyclic AMP; diabetes mellitus; enzyme mechanism; insulin; laboratory mouse; laboratory rat; liver cells; liver metabolism

The mechanism of insulin's regulation of various metabolic pathways remains poorly understood. Insulin acts as a physiologic antagonist of cyclic AMP in many tissues; therefore, it has been hypothesized that insulin may act through calcium as a second messenger. With the discovery of calmodulin, the mechanism of hormonal regulation via activation of the Ca++/calmodulin complex has begun to be recognized. There is further evidence which suggests that the Ca++/calmodulin complex can activate or inactivate certain kinases or phosphatases which appear to be regulated by insulin. We propose to address the hypothesis that insulin acts through a Ca++/calmodulin dependent phosphatase, calcineurin, to modulate the cAMP signal in cells. We will do this by developing an antibody to hepatic calcineurin and studying this enzyme in detail in isolated rat hepatocytes or hepatoma cells variously treated with insulin, glucagon or Beta agonists. These studies will be extended to study the enzyme in livers of streptozotocin-induced diabetic rats and db/db mice. We hope that these studies will further our understanding of insulin action in liver and the pathophysiology of diabetes.

胰岛素调节各种代谢途径的机制尚不清楚

项目成果

Identification of a putative Na(+)-H+ exchanger regulatory cofactor in rabbit renal BBM.

兔肾 BBM 中推定的 Na()-H 交换调节辅因子的鉴定。

• DOI: 10.1152/ajprenal.1990.259.6.f867
• 发表时间: 1990
• 期刊: The American journal of physiology
• 作者: Morell,G;Steplock,D;Shenolikar,S;Weinman,EJ
• 通讯作者: Weinman,EJ

Regulation of the renal Na(+)-H+ exchanger by calcium calmodulin-dependent multifunctional protein kinase II.

钙调蛋白依赖性多功能蛋白激酶 II 调节肾 Na()-H 交换器。

• 发表时间: 1992
• 期刊: Mineral and electrolyte metabolism
• 作者: Weinman,E;Hanley,R;Morell,G;Yuan,N;Steplock,D;Bui,G;Shenolikar,S
• 通讯作者: Shenolikar,S

Identification of the human NHE-1 form of Na(+)-H+ exchanger in rabbit renal brush border membranes.

兔肾刷状缘膜中人 NHE-1 形式 Na()-H 交换剂的鉴定。

• DOI: 10.1172/jci116433
• 发表时间: 1993
• 期刊: The Journal of clinical investigation
• 作者: Weinman,EJ;Steplock,D;Corry,D;Shenolikar,S
• 通讯作者: Shenolikar,S

Identification of calcium-calmodulin multifunctional protein kinase II in rabbit kidney.

• DOI: 10.1038/ki.1990.167
• 发表时间: 1990-07
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: R. Hanley;S. Shenolikar;J. Pollack;D. Steplock;E. Weinman

Chimeric calmodulin-cardiac troponin C proteins differentially activate calmodulin target enzymes.

嵌合钙调蛋白-心肌肌钙蛋白 C 蛋白差异性地激活钙调蛋白靶酶。

• 发表时间: 1990
• 期刊: The Journal of biological chemistry
• 作者: George,SE;VanBerkum,MF;Ono,T;Cook,R;Hanley,RM;Putkey,JA;Means,AR
• 通讯作者: Means,AR