title: 4-Hydroxyisoleucine: A Potential New Treatment for Type 2 Diabetes Mellitus.
abstract: 4-Hydroxyisoleucine (4-HIL) is a compound found in Trigonella foenum-graecum (fenugreek) seeds, which have been used as part of traditional medicine to treat diabetes mellitus. The synthesis of 4-HIL on a large scale is possible using fermentation methods (artificial synthesis) involving the isolation of the L-isoleucine dioxygenase gene from Bacillus thuringiensis, which can yield a greater quantity of 4-HIL than that produced with conventional methods (82 % attained with fermentation methods vs. 0.6-39 % attained with conventional methods). In studies of rats and humans, T. foenum-graecum improved laboratory parameters associated with renal dysfunction and dyslipidemia, increased levels of antioxidants and hormones that are altered in patients with type 2 diabetes mellitus (T2DM), and decreased fasting blood glucose, 2-h postprandial plasma glucose, and glycated hemoglobin. Similarly, in in vitro and preclinical studies, 4-HIL decreased glucose levels, hepatic glucose production, glucose/insulin ratios, indicators of hepatic damage, triglycerides, and total cholesterol, and increased utilization of glucose and levels of high-density lipoprotein cholesterol. Studies in humans are needed to determine whether 4-HIL is safer and more effective than current medications for the treatment of T2DM.
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, People's Republic of China.
authors.forename: Mohammad Ishraq
authors.initials: MI
authors.lastname: Zafar
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, People's Republic of China. gaofengwh@aliyun.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007532:Isoleucine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010946:Plants, Medicinal; D051381:Rats; D029910:Trigonella
chemical_list: C104672:4-hydroxyisoleucine; D000975:Antioxidants; D001786:Blood Glucose; D007532:Isoleucine