Vanadate stimulation of 2-deoxyglucose transport is not mediated by PI 3-kinase in human skeletal muscle.
Glucose transport in mammalian skeletal muscle is stimulated by insulin, hypoxia and tyrosine protein phosphatase inhibitors such as vanadate. However, it is unknown whether the vanadate signaling mechanism shares a common or separate pathway with insulin or hypoxia. Therefore, experiments were conducted on incubated human muscle strips to compare the effects of vanadate with insulin and hypoxia stimulated 2-deoxyglucose 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 demonstrate 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) reduced insulin but not vanadate or hypoxia stimulated 2-DOG transport. Moreover, PI 3-kinase activity was significantly elevated (P < 0.05) in the presence of insulin but not vanadate. In conclusion, these data suggest that vanadate and hypoxia stimulate glucose transport via a similar signaling pathway which is distinct from insulin and that the vanadate signaling pathway is not mediated by PI 3-kinase in human skeletal muscle.
Cortright
R N
RN
Department of Biochemistry, School of Medicine, East Carolina University, Greenville, NC 27858-4354, USA.
Azevedo
J L
JL
Hickey
M S
MS
Tapscott
E B
EB
Dohm
G L
GL
D000704:Analysis of Variance; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D015687:Cell Hypoxia; D003847:Deoxyglucose / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014638:Vanadates / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D014638:Vanadates; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases