Effect of dehydroepiandrosterone on insulin sensitivity in Otsuka Long-Evans Tokushima-fatty rats.
In order to clarify the effect of dehydroepiandrosterone (DHEA) on improvement of insulin resistance, we examined the effects of overexpression of wild-type protein kinase C-zeta (wt-PKCzeta)/3-phosphoinositide-dependent protein kinase-1 (wt-PDK1) and kinase-inactive PKCzeta/PDK1 (DeltaPKCzeta/DeltaPDK1) on DHEA-induced [(3)H]2-deoxyglucose (DOG) uptake using the electroporation method in rat adipocytes. Overexpression of wt-PKCzeta and wt-PDK1 significantly increased in DHEA-induced [(3)H]2-DOG uptake. Wortmannin completely suppressed DHEA-induced [(3)H]2-DOG uptake in wt-PKCzeta- and wt-PDK1-transfected adipocytes. Overexpression of neither DeltaPKCzeta nor DeltaPDK1 increased DHEA-induced [(3)H]2-DOG uptake. Otsuka Long-Evans fatty rats (OLETF), animal models of type 2 diabetes, and Long-Evans Tokushima rats (LETO) as control, were treated with 0.4% DHEA for 2 weeks. Insulin-induced [(3)H]2-DOG uptakes, activations of PI 3-kinase and PKCzeta of adipocytes were significantly increased in DHEA-treated OLETF rats. Moreover, plasma glucose levels in OLETF rats after treatment with DHEA for 2 weeks were significantly lower than treatment without DHEA, but not in LETO rats. These results indicate that DHEA treatment may improve glucose tolerance through a PI 3-kinase-PKCzeta pathway and downregulates adiposity in OLETF rats.
Ishizuka
Tatsuo
T
Department of General Internal Medicine, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan. ishizuka@gifu-u.ac.jp
Miura
Atsushi
A
Kajita
Kazuo
K
Matsumoto
Masami
M
Sugiyama
Chiyo
C
Matsubara
Kenji
K
Ikeda
Takahide
T
Mori
Ichiro
I
Morita
Hiroyuki
H
Uno
Yoshihiro
Y
Mune
Tomoatsu
T
Kanoh
Yoshinori
Y
Ishizawa
Masayoshi
M
D017667:Adipocytes / Q000201:enzymology / Q000637:transplantation; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D018274:Electroporation; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010957:Plasmids; D011493:Protein Kinase C / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D000077191:Wortmannin; D000099221:Protein Kinase C zeta