The Antihyperglycemic Drug a-Lipoic Acid Stimulates Glucose Uptake via Both GLUT4 Translocation and GLUT4 Activation Potential Role of p38 Mitogen-Activated Protein Kinase in GLUT4 Activation

The cofactor of mitochondrial dehydrogenase com-plexes and potent antioxidant a-lipoic acid has been shown to lower blood glucose in diabetic animals. a-Li-poic acid enhances glucose uptake and GLUT1 and GLUT4 translocation in 3T3-L1 adipocytes and L6 myo-tubes, mimicking insulin action. In both cell types, insulin-stimulated glucose uptake is reduced by inhibi-tors of p38 mitogen-activated protein kinase (MAPK). Here we explore the effect of a-lipoic acid on p38 MAPK, phosphatidylinositol (PI) 3-kinase, and Akt1 in L6 myo-tubes. a-Lipoic acid (2.5 mmol/l) increased PI 3-kinase activity (31-fold) and Akt1 (4.9-fold). Both activities were inhibited by 100 nmol/l wortmannin. a-Lipoic acid also stimulated p38 MAPK phosphorylation by twofold within 10 min. The phosphorylation persisted for a