Ishizuka Tatsuo, Miura Atsushi, Kajita Kazuo, Matsumoto Masami, Sugiyama Chiyo, Matsubara Kenji, Ikeda Takahide, Mori Ichiro, Morita Hiroyuki, Uno Yoshihiro, Mune Tomoatsu, Kanoh Yoshinori, Ishizawa Masayoshi
Department of General Internal Medicine, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan.
Acta Diabetol. 2007 Dec;44(4):219-26. doi: 10.1007/s00592-007-0009-4. Epub 2007 Sep 6.
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.
为了阐明脱氢表雄酮（DHEA）对改善胰岛素抵抗的作用，我们采用电穿孔法，研究了野生型蛋白激酶C-ζ（wt-PKCζ）/3-磷酸肌醇依赖性蛋白激酶-1（wt-PDK1）和激酶失活型PKCζ/PDK1（DeltaPKCζ/DeltaPDK1）过表达对DHEA诱导的大鼠脂肪细胞[³H]2-脱氧葡萄糖（DOG）摄取的影响。wt-PKCζ和wt-PDK1的过表达显著增加了DHEA诱导的[³H]2-DOG摄取。渥曼青霉素完全抑制了wt-PKCζ和wt-PDK1转染脂肪细胞中DHEA诱导的[³H]2-DOG摄取。DeltaPKCζ和DeltaPDK1的过表达均未增加DHEA诱导的[³H]2-DOG摄取。将2型糖尿病动物模型大冢Long-Evans肥胖大鼠（OLETF）和作为对照的Long-Evans德岛大鼠（LETO）用0.4% DHEA处理2周。在DHEA处理的OLETF大鼠中，胰岛素诱导的脂肪细胞[³H]2-DOG摄取、PI 3-激酶和PKCζ的激活显著增加。此外，用DHEA处理2周后的OLETF大鼠的血浆葡萄糖水平显著低于未用DHEA处理的大鼠，但LETO大鼠并非如此。这些结果表明，DHEA治疗可能通过PI 3-激酶-PKCζ途径改善葡萄糖耐量，并下调OLETF大鼠的肥胖程度。
