Mechanism of insulin resistance in obesity: a role of ATP

作     者：Jianping Ye Jianping Ye

作者机构：Shanghai Diabetes InstituteShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China 

出 版 物：《Frontiers of Medicine》 (医学前沿（英文版）)

年 卷 期：2021年第15卷第3期

页      面：372-382页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：This work is supported by the National Key R&D Program of China(No.2018YFA0800603) 

主　　题：type 2 diabetes energy expenditure mitochondria hyperinsulinemia hyperglucagonemia AMPK 

摘      要：Obesity increases the risk of type 2 diabetes through the induction of insulin *** mechanism of insulin resistance has been extensively investigated for more than 60 years,but the essential pathogenic signal remains *** hypotheses include inflammation,mitochondrial dysfunction,hyperinsulinemia,hyperglucagonemia,glucotoxicity,and *** discoveries based on these hypotheses are unsuccessful in the development of new *** this review,multidisciplinary literature is integrated to evaluate ATP as a primary signal for insulin *** ATP production is elevated in insulin-sensitive cells under obese conditions independent of energy demand,which we have named“mitochondrial overheating.Overheating occurs because of substrate oversupply to mitochondria,leading to extra ATP *** ATP overproduction contributes to the systemic insulin resistance through several mechanisms,such as inhibition of AMPK,induction of mTOR,hyperinsulinemia,hyperglucagonemia,and mitochondrial *** resistance represents a feedback regulation of energy oversupply in cells to control mitochondrial overloading by *** resistance cuts down the substrate uptake to attenuate mitochondrial *** downregulation of the mitochondrial overloading by medicines,bypass surgeries,calorie restriction,and physical exercise leads to insulin sensitization in ***,ATP may represent the primary signal of insulin resistance in the cellular protective response to the substrate *** prevention of ATP overproduction represents a key strategy for insulin sensitization.