L-4-Hydroxyisoleucine, a natural product isolated and purified from the seeds of Trigonella foenum-graecum L., acts to improve insulin resistance by promoting mitochondrial biogenesis in high fructose diet fed STZ induced diabetic rats.
L-4-Hydroxyisoleucine (4-HIL) is a new type of insulin secretion enhancer and can be used in the treatment of type 2 diabetes. L-4-hydroxyisoleucine is a non-protein amino acid in fenugreek. This amino acid mainly exists in fenugreek seeds, accounting for about 80% of the total free amino acids in the seeds. 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L-isoleucine still accumulated in the culture[3]. 4-HIL significantly repressed the mRNA and protein levels of iRhom2 and TACE in RAW264.7 macrophages after LPS stimulated. Meanwhile, the levels of pro-inflammatory cytokines, including TNF-α, MCP-1, and IL-6, were substantially suppressed by 4-HIL in the co-culture system[4]. 4-HIL directly or indirectly reversed TNF-α reduced glycogen levels by inhibiting JNK and IRS-1 (Ser(307)) phosphorylation and increasing AKT (Ser(473)) and GSK-3 phosphorylation[5].
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