DHEA, Insulin Sensitivity, and Adiposity

Acta Diabetol. 2007 Sep 6; [Epub ahead of print]

Effect of dehydroepiandrosterone on insulin sensitivity in Otsuka
Long-Evans Tokushima-fatty rats.

Ishizuka T, Miura A, Kajita K, Matsumoto M, Sugiyama C, Matsubara K,
Ikeda T, Mori I, Morita H, Uno Y, Mune T, Kanoh Y, Ishizawa M.

Department of General Internal Medicine, Gifu University Graduate
School of Medicine, Yanagido 1-1, Gifu, 501-1194, Japan

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.
.

Relevant Pages