title: 4-Hydroxyisoleucine improves insulin resistance by promoting mitochondrial biogenesis and act through AMPK and Akt dependent pathway.
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.
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226 031, India.
authors.forename: Arun Kumar
authors.initials: AK
authors.lastname: Rawat
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 031, India.
authors.forename: Venkateswarlu
authors.initials: V
authors.lastname: Korthikunta
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226 031, India.
authors.forename: Sudeep
authors.initials: S
authors.lastname: Gautam
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226 031, India.
authors.forename: Savita
authors.initials: S
authors.lastname: Pal
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 031, India.
authors.forename: Narender
authors.initials: N
authors.lastname: Tadigoppula
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226 031, India.
authors.forename: Akhilesh Kumar
authors.initials: AK
authors.lastname: Tamrakar
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226 031, India. Electronic address: drarv55cdri@rediffmail.com.
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Srivastava
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005786:Gene Expression Regulation; D007333:Insulin Resistance; D007532:Isoleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C104672:4-hydroxyisoleucine; D001786:Blood Glucose; D007532:Isoleucine; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases
keywords: 4-Hydroxyisoleucine; Glucose tolerance; Insulin resistance; L6 myotube; Mitochondrial biogenesis