Effect of vanadate and insulin on glucose transport in isolated adult rat cardiomyocytes

It is now widely accepted that insulin stimulation of glucose uptake by mus cle cells is due to the activation of protein kinase B, leading to the recr uitment of glucose transporter proteins from an intracellular compartment t o the plasma membrane. Vanadate is a protein tyrosine phosphatase (PTP) inh ibitor and a known insulin mimetic agent. Vanadate causes an increase of gl ucose transport in various tissues, but the mechanism of stimulation is not clearly understood. Hence in the present study, we have compared the mecha nism of 2-deoxy-D-glucose transport induced by vanadate and insulin in isol ated rat cardiomyocytes. Vanadate stimulated deoxyglucose transport in a ti me- and concentration-dependent manner. Insulin (100 nM) and vanadate (5 mM ) stimulated 2-deoxy-D-glucose transport on an average by 3- and 2-fold res pectively over basal values. The stimulation of glucose transport was accom panied by an activation of protein kinase B (PKB). This study also revealed that the activation of PKB and stimulation of 2-deoxyglucose uptake by van adate and insulin are inhibited by treatment with wortmannin, a specific in hibitor of phoshatidylinositol 3-kinase (PI 3-kinase). Hence, we conclude t hat both insulin and vanadate follow the same signalling pathway downstream of PI 3-kinase to stimulate 2-deoxy-D-glucose transport.