INSULIN-STIMULATED PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY AND 2-DEOXY-D-GLUCOSE UPTAKE IN RAT SKELETAL-MUSCLES

To date there is suggestive evidence that phosphatidylinositol 3-kinas e participates in insulin-stimulated glucose transport. However, its i nvolvement in skeletal muscle, a major site of insulin-stimulated gluc ose disposal, has not been addressed. Therefore, we tested the effects of wortmannin, a known inhibitor of phosphatidylinositol 3-kinase, on insulin-stimulated 2-deoxyglucose uptake by rat soleus muscle in vitr o. Wortmannin (1 mu M) reversibly inhibited insulin-induced 2-deoxyglu cose uptake in so[eus muscle by 44%. Inclusion of 5 mu M wortmannin in the incubation medium completely abolished the insulin-induced increm ent in 2-deoxyglucose uptake. In conclusion, the results are consisten t with the concept that phosphatidylinositol 3-kinase plays a role in the insulin-signaling cascade linking insulin-receptor tyrosine kinase activation to glucose uptake in skeletal muscle. (C) 1995 Academic Pr ess, Inc.