Fu Qin, Shi Qian, West Toni M, Xiang Yang K
*Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; †The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China; ‡Department of Pharmacology, University of California at Davis, Davis, CA; §VA Northern California Healthcare System, Mather, CA.
J Cardiovasc Pharmacol. 2017 Aug;70(2):74-86. doi: 10.1097/FJC.0000000000000481.
Diabetes is a major risk factor for the development of heart failure. One of the hallmarks of diabetes is insulin resistance associated with hyperinsulinemia. The literature shows that insulin and adrenergic signaling is intimately linked to each other; however, whether and how insulin may modulate cardiac adrenergic signaling and cardiac function remains unknown. Notably, recent studies have revealed that insulin receptor and β2 adrenergic receptor (β2AR) forms a membrane complex in animal hearts, bringing together the direct contact between 2 receptor signaling systems, and forming an integrated and dynamic network. Moreover, insulin can drive cardiac adrenergic desensitization via protein kinase A and G protein-receptor kinases phosphorylation of the β2AR, which compromises adrenergic regulation of cardiac contractile function. In this review, we will explore the current state of knowledge linking insulin and G protein-coupled receptor signaling, especially β-adrenergic receptor signaling in the heart, with emphasis on molecular insights regarding its role in diabetic cardiomyopathy.
糖尿病是心力衰竭发生的主要危险因素。糖尿病的一个标志是与高胰岛素血症相关的胰岛素抵抗。文献表明胰岛素信号与肾上腺素能信号密切相关；然而，胰岛素是否以及如何调节心脏肾上腺素能信号和心脏功能仍不清楚。值得注意的是，最近的研究表明，胰岛素受体和β2肾上腺素能受体（β2AR）在动物心脏中形成膜复合物，使两个受体信号系统直接接触，形成一个整合的动态网络。此外，胰岛素可通过蛋白激酶A和G蛋白偶联受体激酶对β2AR的磷酸化作用，导致心脏肾上腺素能脱敏，从而损害心脏收缩功能的肾上腺素能调节。在这篇综述中，我们将探讨胰岛素与G蛋白偶联受体信号，特别是心脏β-肾上腺素能受体信号之间联系的当前知识状态，重点是其在糖尿病性心肌病中作用的分子见解。
