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胰岛素抵抗的生化及分子基础

Biochemical and molecular basis of insulin resistance.

作者信息

Chakraborty Chiranjib

机构信息

Institute of Applied Medicines and Research, 9th Miles-tone, Ghaziabad, UP, India.

出版信息

Curr Protein Pept Sci. 2006 Apr;7(2):113-21. doi: 10.2174/138920306776359759.

Abstract

Insulin-resistance is a major problem associated with diabetes and that is increasing rapidly worldwide. Insulin is a peptide hormone secreted by the beta-cells of the pancreatic islets of Langerhans in response to increased circulating levels of glucose and amino acids and it is essential for appropriate tissue development, growth, and maintenance of whole-body glucose homeostasis by regulating carbohydrate, lipid and protein metabolism. Insulin resistance is a defect in signal transduction. The signaling mechanisms involved in the various biologic responses to insulin remain somewhat elusive. This review focuses on the structure and activity of insulin receptor, inheritance of insulin resistance, insulin receptor and alleles, enzyme activity in insulin resistance, insulin receptor in phosphorylation and relating substrate. We have discussed insulin receptor substrate-family (IRS) related to insulin resistance, detail downstream signaling effects, GLUT4 vesicle translocation and related events, cytokine-mediated insulin resistance, and feedback control mechanisms. This review also focuses on insulin resistance in obesity-linked metabolic syndrome, insulin resistance related to plasma membrane disturbances and insulin resistance for exercise and cellular integrity. Finally, we can conclude that insulin resistance is really a complex phenomenon in which several genetic defects combine with environmental stresses.

摘要

胰岛素抵抗是与糖尿病相关的一个主要问题,并且在全球范围内正迅速增加。胰岛素是一种肽类激素,由胰岛β细胞分泌,以应对循环中葡萄糖和氨基酸水平的升高,它对于通过调节碳水化合物、脂质和蛋白质代谢来实现适当的组织发育、生长以及维持全身葡萄糖稳态至关重要。胰岛素抵抗是信号转导中的一种缺陷。参与胰岛素各种生物学反应的信号传导机制仍有些难以捉摸。本综述重点关注胰岛素受体的结构与活性、胰岛素抵抗的遗传、胰岛素受体及其等位基因、胰岛素抵抗中的酶活性、胰岛素受体的磷酸化及其相关底物。我们讨论了与胰岛素抵抗相关的胰岛素受体底物家族(IRS)、详细的下游信号效应、GLUT4囊泡转运及相关事件、细胞因子介导的胰岛素抵抗以及反馈控制机制。本综述还重点关注肥胖相关代谢综合征中的胰岛素抵抗、与质膜紊乱相关的胰岛素抵抗以及运动和细胞完整性方面的胰岛素抵抗。最后,我们可以得出结论,胰岛素抵抗确实是一种复杂的现象,其中多种遗传缺陷与环境压力相互作用。

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