Vanadate fully stimulates insulin receptor substrate-1 associated phosphatidyl inositol 3-kinase activity in adipocytes from young and old rats.
Vanadate stimulates adipocyte 2-deoxyglucose transport and GLUT-4 translocation to the membrane through an insulin receptor-independent but wortmannin-inhibitable pathway. Vanadate stimulates PI 3-kinase in anti-IRS-1 immunoprecipitates and the binding between IRS-1 and the p85alpha subunit of PI 3-kinase. In insulin-resistant adipocytes from old rats vanadate fully stimulates IRS-1-associated PI 3-kinase, but partially activates glucose uptake. We conclude that: (a) vanadate stimulates 2-deoxyglucose uptake using a pathway that converges with that of insulin at the level of PI 3-kinase; and (b) adipocytes from old rats are defective in the insulin pathway at steps located both upstream and downstream of PI 3-kinase.
Molero
J C
JC
Departamento de Biología Molecular, Centro de Biología Molecular (CSIC), Facultad de Ciencias, Universidad Autónoma, Cantoblanco, Madrid, Spain.
Martínez
C
C
Andrés
A
A
Satrústegui
J
J
Carrascosa
J M
JM
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004789:Enzyme Activation; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014638:Vanadates / Q000494:pharmacology*
D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; C495694:Slc2a4 protein, rat; D014638:Vanadates; D003847:Deoxyglucose; D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases