DHEA improves glucose uptake via activations of protein kinase C and phosphatidylinositol 3-kinase.
We have examined the effect of adrenal androgen, dehydroepiandrosterone (DHEA), on glucose uptake, phosphatidylinositol (PI) 3-kinase, and protein kinase C (PKC) activity in rat adipocytes. DHEA (1 microM) provoked a twofold increase in 2-[3H]deoxyglucose (DG) uptake for 30 min. Pretreatment with DHEA increased insulin-induced 2-[3H]DG uptake without alterations of insulin specific binding and autophosphorylation of insulin receptor. DHEA also stimulated PI 3-kinase activity. [3H]DHEA bound to purified PKC containing PKC-alpha, -beta, and -gamma. DHEA provoked the translocation of PKC-beta and -zeta from the cytosol to the membrane in rat adipocytes. These results suggest that DHEA stimulates both PI 3-kinase and PKCs and subsequently stimulates 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% DHEA for 2 wk. Insulin- and 12-O-tetradecanoyl phorbol-13-acetate-induced 2-[3H]DG uptakes of adipocytes were significantly increased, but there was no significant increase in the soleus muscles in DHEA-treated GK/Wistar or OLETF/Long-Evans Tokushima (LETO) rats when compared with untreated GK/Wistar or OLETF/LETO rats. These results indicate that in vivo DHEA treatment can result in increased insulin-induced glucose uptake in two different NIDDM rat models.
Ishizuka
T
T
The Third Department of Internal Medicine, Gifu University School of Medicine, Gifu 500, Japan.
Kajita
K
K
Miura
A
A
Ishizawa
M
M
Kanoh
Y
Y
Itaya
S
S
Kimura
M
M
Muto
N
N
Mune
T
T
Morita
H
H
Yasuda
K
K
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D003687:Dehydroepiandrosterone / Q000378:metabolism / Q000494:pharmacology*; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004075:Diglycerides / Q000096:biosynthesis; D004789:Enzyme Activation / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D020334:Rats, Inbred OLETF; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D007328:Insulin; D003687:Dehydroepiandrosterone; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate