过刊浏览

支链氨基酸及代谢中间产物对胰岛素抵抗的调控及其机制

白丹丹, 肖卫华^*

上海体育学院上海市人类运动能力开发与保障重点实验室，“运动健身科技”省部共建教育部重点实验室，上海 200438

摘要

支链氨基酸作为必需氨基酸，可用于合成含氮化合物，也可充当信号分子调节物质代谢。研究表明，支链氨基酸水平升高与胰岛素抵抗和2型糖尿病发生密切相关，其可通过激活哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)信号通路来影响胰岛素信号转导，还可通过损害脂质代谢和影响线粒体功能来调控胰岛素抵抗。此外，支链氨基酸分解代谢异常会导致代谢中间产物(如支链α-酮酸、3-羟基异丁酸和β-氨基异丁酸等)积累，其中支链α-酮酸和3-羟基异丁酸可通过影响胰岛素信号通路、损害脂质代谢等来诱发胰岛素抵抗，而β-氨基异丁酸可通过减少脂质积聚和炎症反应、增强脂肪酸氧化等来改善胰岛素抵抗。本文系统综述了支链氨基酸及其代谢中间产物对胰岛素抵抗的影响及调控机制，以期为胰岛素抵抗和2型糖尿病的防治提供新方向。

关键词： 支链氨基酸; 代谢中间产物; 胰岛素抵抗

Regulatory effects and mechanisms of branched chain amino acids and metabolic intermediates on insulin resistance

BAI Dan-Dan, XIAO Wei-Hua^*

Shanghai Key Laboratory of Human Performance, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China

Abstract

Branched chain amino acids, as essential amino acids, can be used to synthesize nitrogen-containing compounds and also act as signal molecules to regulate substance metabolism. Studies have shown that the elevated level of branched chain amino acids is closely related to insulin resistance and type 2 diabetes. It can affect insulin signal transduction by activating mammalian target of rapamycin (mTOR) signal pathway, and regulate insulin resistance by damaging lipid metabolism and affecting mitochondrial function. In addition, abnormal catabolism of branched amino acids can lead to the accumulation of metabolic intermediates, such as branched chain α-keto acids, 3-hydroxyisobutyrate and β-aminoisobutyric acid. Branched chain α-keto acids and 3-hydroxyisobutyrate can induce insulin resistance by affecting insulin signaling pathway and damaging lipid metabolism. β-aminoisobutyric acid can improve insulin resistance by reducing lipid accumulation and inflammatory reaction and enhancing fatty acid oxidation. This paper systematically reviewed the regulatory effects and mechanisms of branched chain amino acids and their metabolic intermediates on insulin resistance, which will provide a new direction for the prevention and treatment of insulin resistance and type 2 diabetes.

Key words: branched chain amino acids; metabolic intermediates; insulin resistance

收稿日期：　　录用日期：

通讯作者：肖卫华　　E-mail: xiaoweihua@sus.edu.cn

DOI: 10.13294/j.aps.2023.0023

引用本文：

白丹丹, 肖卫华. 支链氨基酸及代谢中间产物对胰岛素抵抗的调控及其机制[J]. 生理学报 2023; 75 (2): 291-302.

BAI Dan-Dan, XIAO Wei-Hua. Regulatory effects and mechanisms of branched chain amino acids and metabolic intermediates on insulin resistance. Acta Physiol Sin 2023; 75 (2): 291-302 (in Chinese with English abstract).