4-Hydroxyisoleucine improves insulin resistance by promoting mitochondrial biogenesis and act through AMPK and Akt dependent pathway |
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| Institution: | 1. Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226 031, India;2. Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 031, India;1. Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA;2. Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, China;3. College of Life Science, Longyan University, Longyan, Fujian, P. R. China;4. Fujian Provincial Key Laboratory for the Prevention and Control of Animal Infectious Diseases and Biotechnology, Longyan, Fujian, P.R. China;5. Key Laboratory of Preventive Veterinary Medicine and Biotechnology (Longyan University), Fujian Province University, Longyan, Fujian, P.R. China;6. Department of Statistics, Florida State University, Tallahassee, FL, USA |
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| Abstract: | 4-Hydroxyisoleucine (4-HIL) is an unusual amino acid isolated from fenugreek seeds (Trigonella foenum graecum L). Various studies have shown that it acts as an antidiabetic agent yet its mechanism of action is not clear. We therefore investigated the effect 4-HIL on the high fructose diet fed streptozotocin induced diabetic rats and L6 myotubes. 4-HIL (50 mg/kg) has improved blood lipid profile, glucose tolerance and insulin sensitivity in a diabetic rat model. It has increased the glucose uptake in L6 myotubes in AMPK-dependent manner and upregulated the expression of genes (PGC-1α, PGC-1β, CPT 1 and CPT 2), which have role in mitochondrial biogenesis and energy metabolism in the liver, skeletal muscles as well as in L6 myotubes. Interestingly, it also increased the AMPK and Akt expression along with their phosphorylated forms in the liver and muscle tissues of treated animals. Altogether we concluded that 4-HIL acts to improve insulin resistance by promoting mitochondrial biogenesis in high fructose diet fed STZ induced diabetic rats. |
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