4-hydroxyisoleucine

**4-hydroxyisoleucine** is a non-proteinogenic amino acid found naturally in the seeds of Trigonella foenum-graecum (fenugreek). It has been studied for its insulinotropic and anti-obesity properties. Mechanistically, 4-hydroxyisoleucine increases glucose-induced insulin secretion from pancreatic beta cells in a strictly glucose-dependent manner and improves insulin sensitivity in peripheral tissues by activating insulin receptor substrate-associated phosphoinositide-3 kinase activity. Preclinical studies have shown that it can reduce fasting blood glucose levels, hepatic glucose production, triglycerides, total cholesterol, and body weight while increasing HDL cholesterol. It is being investigated as a potential treatment for metabolic syndrome components such as type 2 diabetes mellitus (T2DM), obesity, and dyslipidemia[1][5][9]. Large-scale synthesis is possible via fermentation using genetically engineered Bacillus thuringiensis[1]. Human clinical data are limited; most evidence comes from animal models or in vitro studies.

Other names

4-HIL(4S)-4-hydroxy-L-isoleucine(2S,3R,4S)-2-amino-4-hydroxy-3-methylpentanoic acidhydroxyisoleucine