Avalos-Soriano Anaguiven, De la Cruz-Cordero Ricardo, Rosado Jorge L, Garcia-Gasca Teresa
Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Juriquilla, Querétaro, Qro. 76230, Mexico.
Nucitec S.A. de C.V. Querétaro, Qro. 76215, Mexico.
Molecules. 2016 Nov 22;21(11):1596. doi: 10.3390/molecules21111596.
Obesity and insulin resistance (IR) are interdependent multifactorial processes that cannot be understood separately. Obesity leads to systemic inflammation and increased levels of free fatty acids that provoke IR and lipotoxicity. At the same time, IR exacerbates adipose cell dysfunction, resulting in chronic inflammation and major lipotoxic effects on nonadipose tissues. 4-Hydroxyisoleucine (4-OHIle), a peculiar nonprotein amino acid isolated from fenugreek () seeds, exhibits interesting effects on IR related to obesity. 4-OHIle increases glucose-induced insulin release, and the insulin response mediated by 4-OHIle depends on glucose concentration. The beneficial effects observed are related to the regulation of blood glucose, plasma triglycerides, total cholesterol, free fatty acid levels, and the improvement of liver function. The mechanism of action is related to increased Akt phosphorylation and reduced activation of Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB. Here, we present a review of the research regarding the insulinotropic and insulin-sensitising activity of 4-OHIle in in vitro and in vivo models.
肥胖与胰岛素抵抗（IR）是相互依存的多因素过程，不能孤立地理解。肥胖会导致全身炎症以及游离脂肪酸水平升高，进而引发胰岛素抵抗和脂毒性。同时，胰岛素抵抗会加剧脂肪细胞功能障碍，导致慢性炎症以及对非脂肪组织产生主要的脂毒性作用。4-羟基异亮氨酸（4-OHIle）是从葫芦巴种子中分离出的一种特殊的非蛋白质氨基酸，对与肥胖相关的胰岛素抵抗具有有趣的作用。4-羟基异亮氨酸可增加葡萄糖诱导的胰岛素释放，且4-羟基异亮氨酸介导的胰岛素反应取决于葡萄糖浓度。观察到的有益作用与血糖、血浆甘油三酯、总胆固醇、游离脂肪酸水平的调节以及肝功能的改善有关。其作用机制与Akt磷酸化增加以及Jun氨基末端激酶（JNK）1/2、细胞外信号调节激酶（ERK）1/2、p38丝裂原活化蛋白激酶（MAPK）和核因子（NF）-κB的激活减少有关。在此，我们对4-羟基异亮氨酸在体外和体内模型中的促胰岛素分泌和胰岛素增敏活性的研究进行综述。
