VANADATE STIMULATION OF 2-DEOXYGLUCOSE TRANSPORT IS NOT MEDIATED BY PI3-KINASE IN HUMAN SKELETAL-MUSCLE

Glucose transport in mammalian skeletal muscle is stimulated by insuli n, hypoxia and tyrosine protein phosphatase inhibitors such as vanadat e. However, it is unknown whether the vanadate signaling mechanism sha res a common or separate pathway with insulin or hypoxia. Therefore, e xperiments were conducted on incubated human muscle strips to compare the effects of vanadate with insulin and hypoxia stimulated 7-deoxyglu cose transport (2-DOG). We also used the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin to examine whether PI 3-kinase is a common step by which each stimulate glucose transport. Results demon strate that whereas the effects of vanadate and hypoxia were additive with insulin stimulated glucose transport, the effect of vanadate plus hypoxia was not. In addition, wortmannin significantly (P < 0.05) red uced insulin but not vanadate or hypoxia stimulated 2-DOG transport. M oreover, PI 3-kinase activity was significantly elevated (P < 0.05) in the presence of insulin but not vanadate. In conclusion, these data s uggest that vanadate and hypoxia stimulate glucose transport via a sim ilar signaling pathway which is distinct from insulin and that the van adate signaling pathway is not mediated by PI3-kinase in human skeleta l muscle. (C) 1997 Elsevier Science B.V.