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 (50mg/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 liver, skeletal muscles as well as in L6 myotubes. Interestingly, it also increased the AMPK and Akt expression along with their phosphorylated forms in liver and muscle tissues of treated animals. Altogether we concluded that 4-HIL act to improve insulin resistance by promoting mitochondrial biogenesis in high fructose diet fed STZ induced diabetic rats.