DHEA improves glucose uptake via activations of protein kinase C and phosphatidylinositol 3-kinase

We have examined the effect of adrenal androgen, dehydroepiandrosterone (DH EA), on glucose uptake, phosphatidylinositol (PI) S-kinase, and protein kin ase C (PKC) activity in rat adipocytes. DHEA (1 mu M) provoked a twofold in crease in 2-[H-3]deoxyglucose (DCT) uptake for 30 min. Pretreatment with DH EA increased insulin-induced 2-[H-3]DG uptake without alterations of insuli n specific binding and autophosphorylation of insulin receptor. DHEA also s timulated PI S-kinase activity. [H-3]DHEA bound to purified PKC containing PKC-alpha, -beta, and -gamma. DHEA provoked the translocation of PKC-beta a nd -zeta from the cytosol to the membrane in rat adipocytes. These results suggest that DHEA stimulates both PI 3-kinase and PKCs and subsequently sti mulates glucose uptake. Moreover, to clarify the in vivo effect of DHEA on Goto-Kakizaki (GK) and Otsuka Long-Evans fatty (OLETF) rats, animal models of non-insulin-dependent diabetes mellitus (NIDDM) were treated with 0.4% D HEA for 2 wk. Insulin- and 12-O-tetradecanoyl phorbol-13-acetate-induced 2- [H-3]DG uptakes of adipocytes were significantly increased, but there was n o significant increase in the soleus muscles in DHEA-treated GK/Wistar or O LETF/Long-Evans Tokushima (LETO) rats when compared with untreated GK/Wista r or OLETF/LETO rats. These results indicate that in vivo DHEA treatment ca n result in increased insulin-induced glucose uptake in two different NIDDM rat models.