Shou Jian, Chen Pei-Jie, Xiao Wei-Hua
School of Kinesiology, Shanghai University of Sport.
J Nutr Sci Vitaminol (Tokyo). 2019;65(5):383-389. doi: 10.3177/jnsv.65.383.
The toxic catabolic intermediates of branched chain amino acids can cause insulin resistance, and are involved in different mechanisms in different metabolic tissues. In skeletal muscle, 3-hydroxy-isobutyrate produced by valine promotes skeletal muscle fatty acid uptake, resulting in the accumulation of incompletely oxidized lipids in skeletal muscle, causing skeletal muscle insulin resistance. In the liver, branched-chain α-keto acids decompose in large amounts, promote hepatic gluconeogenesis, and lead to the accumulation of multiple acylcarnitines, which damages the mitochondrial tricarboxylic acid cycle, resulting in the accumulation of incomplete oxidation products, oxidative stress in mitochondria, and hepatic insulin resistance. In adipose tissue, the expression of branched-chain amino acid catabolic enzymes (branched-chain amino acid transaminase, branched-chain α-keto acid dehydrogenase) is reduced, resulting in an increased level of plasma branched-chain amino acids, thereby causing massive decomposition of branched-chain amino acids in tissues such as skeletal muscle and liver, and inducing insulin resistance. However, branched-chain amino acids, as a common nutritional supplement for athletes, do not induce insulin resistance. A possible explanation for this phenomenon is that exercise can enhance the mitochondrial oxidative potential of branched-chain amino acids, alleviate or even eliminate the accumulation of branched-chain amino acid catabolic intermediates, and promotes branched-chain amino acids catabolism into beta-aminoisobutyric acid, increasing plasma beta-aminoisobutyric acid concentration, improving insulin resistance. This article reveals the mechanism of BCAA-induced insulin resistance and the relationship between exercise and BCAAs metabolism, adds a guarantee for the use of BCAAs, and provides a new explanation for the occurrence of diabetes and how exercise improves diabetes.
支链氨基酸的毒性分解代谢中间体可导致胰岛素抵抗，并在不同代谢组织中涉及不同机制。在骨骼肌中，缬氨酸产生的3-羟基异丁酸促进骨骼肌脂肪酸摄取，导致骨骼肌中不完全氧化脂质的积累，引起骨骼肌胰岛素抵抗。在肝脏中，支链α-酮酸大量分解，促进肝糖异生，并导致多种酰基肉碱积累，损害线粒体三羧酸循环，导致不完全氧化产物积累、线粒体氧化应激和肝胰岛素抵抗。在脂肪组织中，支链氨基酸分解代谢酶（支链氨基酸转氨酶、支链α-酮酸脱氢酶）的表达降低，导致血浆支链氨基酸水平升高，从而导致骨骼肌和肝脏等组织中支链氨基酸大量分解，并诱导胰岛素抵抗。然而，支链氨基酸作为运动员常用的营养补充剂，并不会诱导胰岛素抵抗。对此现象的一种可能解释是，运动可增强支链氨基酸的线粒体氧化潜能，减轻甚至消除支链氨基酸分解代谢中间体的积累，并促进支链氨基酸分解为β-氨基异丁酸，增加血浆β-氨基异丁酸浓度，改善胰岛素抵抗。本文揭示了支链氨基酸诱导胰岛素抵抗的机制以及运动与支链氨基酸代谢之间的关系，为支链氨基酸的使用增添了保障，并为糖尿病的发生以及运动如何改善糖尿病提供了新的解释。
