Jetté Lucie, Harvey Laurent, Eugeni Karen, Levens Nigel
BELLUS Health Inc, 275 Boulevard Armand-Frappier, Laval, Quebec H7V 4A7, QC, Canada.
Curr Opin Investig Drugs. 2009 Apr;10(4):353-8.
The plant fenugreek has been used for centuries as a treatment for diabetes. This article presents evidence that the major isomer of 4-hydroxyisoleucine, an atypical branched-chain amino acid derived from fenugreek, is responsible for the effects of this plant on glucose and lipid metabolism. 4-Hydroxyisoleucine was demonstrated to stimulate glucose-dependent insulin secretion by a direct effect on pancreatic islets. In addition to stimulating insulin secretion, 4-hydroxyisoleucine reduced insulin resistance in muscle and/or liver by activating insulin receptor substrate-associated phosphoinositide 3 (PI3) kinase activity. 4-Hydroxyisoleucine also reduced body weight in diet-induced obese mice. The decrease in body weight was associated with a marked decrease in both plasma insulin and glucose levels, both of which are elevated in this animal model. Finally, 4-hydroxyisoleucine decreased elevated plasma triglyceride and total cholesterol levels in a hamster model of diabetes. Based on the beneficial metabolic properties that have been demonstrated, 4-hydroxyisoleucine, a simple, plant-derived amino acid, may represent an attractive new candidate for the treatment of type 2 diabetes, obesity and dyslipidemia, all key components of metabolic syndrome.
胡芦巴这种植物几个世纪以来一直被用于治疗糖尿病。本文提供的证据表明，4-羟基异亮氨酸（一种源自胡芦巴的非典型支链氨基酸）的主要异构体，是这种植物对葡萄糖和脂质代谢产生作用的原因。已证实4-羟基异亮氨酸通过对胰岛的直接作用来刺激葡萄糖依赖性胰岛素分泌。除了刺激胰岛素分泌外，4-羟基异亮氨酸还通过激活胰岛素受体底物相关的磷酸肌醇3（PI3）激酶活性，降低肌肉和/或肝脏中的胰岛素抵抗。4-羟基异亮氨酸还能降低饮食诱导的肥胖小鼠的体重。体重减轻与血浆胰岛素和葡萄糖水平的显著降低有关，在这种动物模型中，这两种物质的水平都会升高。最后，在糖尿病仓鼠模型中，4-羟基异亮氨酸降低了升高的血浆甘油三酯和总胆固醇水平。基于已证实的有益代谢特性，4-羟基异亮氨酸这种简单的、源自植物的氨基酸，可能是治疗2型糖尿病、肥胖症和血脂异常（代谢综合征的所有关键组成部分）的一个有吸引力的新候选药物。
