Thiazolidinedione treatment enhances insulin effects on protein kinase C-zeta/lambda activation and glucose transport in adipocytes of nondiabetic and Goto-Kakizaki type II diabetic rats

We evaluated effects of the thiazolidinedione, rosiglitazone, on insulin-in duced activation of protein kinase C (PRC)-zeta/lambda and glucose transpor t in adipocytes of Goto-Kakizaki (GK)-diabetic and nondiabetic rats. Insuli n effects on PKC-zeta/lambda and alpha-deoxyglucose uptake were diminished by approximately 50% in GK adipocytes, as compared with control adipocytes. This defect in insulin-induced PKC-zeta/lambda activation was associated w ith diminished activation of IRS-1-dependent phosphatidylinositol (PI) 3-ki nase, and was accompanied by diminished phosphorylation of threonine 410 in the activation loop of PRC-zeta; in contrast, protein kinase B (PKB) activ ation and phosphorylation were not significantly altered, Rosiglitazone com pletely reversed defects in insulin-stimulated 2-deoxyglucose uptake, PKC z eta/lambda enzyme activity and PKC-zeta threonine 410 phosphorylation, but had no effect on PI 3-kinase activation or PKB activation/phosphorylation i n GK adipocytes. Similarly, in adipocytes of nondiabetic rats, rosiglitazon e provoked increases in insulin-stimulated 2-deoxyglucose uptake, PKC-zeta/ lambda enzyme activity and phosphorylation of both threonine 410 activation loop and threonine 560 auto-phosphorylation sites in PKC-zeta, but had no effect on PI 3-kinase activation or PKB activation/phosphorylation. Our fin dings suggest that (a) decreased effects of insulin on glucose transport in adipocytes of GK diabetic rats are due at least in part to diminished phos phorylation/ activation of PKC-zeta/lambda, and (b) thiazolidinediones enha nce glucose transport responses to insulin in adipocytes of both diabetic a nd nondiabetic rats through increases in phosphorylation/activation of PKC- zeta/lambda.