4-Hydroxyisoleucine stimulates glucose uptake by increasing surface GLUT4 level in skeletal muscle cells via phosphatidylinositol-3-kinase-dependent pathway

• Published in: European journal of nutrition 2012-10, Vol.51 (7), p.893-898
• Main Authors: Jaiswal, Natasha, Maurya, Chandan K., Venkateswarlu, K., Sukanya, P., Srivastava, Arvind K., Narender, Tadigoppula, Tamrakar, Akhilesh K.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cattle; Cell Membrane - drug effects; Chemistry; Chemistry and Materials Science; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Glucose - pharmacokinetics; Glucose Transporter Type 1 - genetics; Glucose Transporter Type 1 - metabolism; Glucose Transporter Type 4 - genetics; Glucose Transporter Type 4 - metabolism; Insulin - metabolism; Isoleucine - analogs & derivatives; Isoleucine - pharmacology; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Nutrition; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Plant Extracts - pharmacology; Protein Transport - drug effects; Rats; RNA, Messenger - genetics; RNA, Messenger - metabolism; Seeds - chemistry; Short Communication; Signal Transduction; Striated muscle. Tendons; Trigonella - chemistry; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 1436-6207; 1436-6215
• DOI: 10.1007/s00394-012-0374-9

Purpose To determine the effect of 4-Hydroxyisoleucine (4-HIL), an unusual amino acid isolated from the seeds of Trigonella foenum - graecum , on glucose uptake and the translocation of glucose transporter 4 (GLUT4) to plasma membrane in skeletal muscle cells and to investigate the underlying mechanisms of action. Methods Rat skeletal muscle cells (L6-GLUT4 myc ) were treated with 4-HIL, and the effect on glucose uptake was determined by measuring the incorporation of radio-labeled 2-deoxy-[ 3 H]- d -glucose (2-DG) into the cell. Translocation of GLUT4 myc to plasma membrane was measured by an antibody-coupled colorimetric assay. Results The prolonged exposure (16 h) of L6-GLUT4 myc myotubes to 4-HIL caused a substantial increase in the 2-DG uptake and GLUT4 translocation to the cell surface, without changing the total amount of GLUT4 and GLUT1. Cycloheximide treatment reversed the effect of 4-HIL on GLUT4 translocation to the basal level suggesting the requirement of new protein synthesis. The 4-HIL-induced increase in GLUT4 translocation was completely abolished by wortmannin, and 4-HIL significantly increased the basal phosphorylation of AKT (Ser-473), but did not change the mRNA expression of AKT, IRS-1, GLUT4, and GSK3β. Conclusion Results suggest that 4-HIL stimulates glucose uptake in L6-GLUT4 myc myotubes by enhancing translocation of GLUT4 to the cell surface in a PI-3-kinase/AKT-dependent mechanism.