Effect of dehydroepiandrosterone on insulin sensitivity in Otsuka Long-Evans Tokushima-fatty rats |
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Authors: | Tatsuo Ishizuka Atsushi Miura Kazuo Kajita Masami Matsumoto Chiyo Sugiyama Kenji Matsubara Takahide Ikeda Ichiro Mori Hiroyuki Morita Yoshihiro Uno Tomoatsu Mune Yoshinori Kanoh Masayoshi Ishizawa |
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Institution: | (1) Department of General Internal Medicine, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan;(2) Department of Endocrinology and Metabolism, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan |
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Abstract: | 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-ζ (wt-PKCζ)/3-phosphoinositide-dependent protein kinase-1 (wt-PDK1) and kinase-inactive
PKCζ/PDK1 (ΔPKCζ/ΔPDK1) on DHEA-induced 3H]2-deoxyglucose (DOG) uptake using the electroporation method in rat adipocytes. Overexpression of wt-PKCζ and wt-PDK1 significantly
increased in DHEA-induced 3H]2-DOG uptake. Wortmannin completely suppressed DHEA-induced 3H]2-DOG uptake in wt-PKCζ- and wt-PDK1-transfected adipocytes. Overexpression of neither ΔPKCζ nor ΔPDK1 increased DHEA-induced
3H]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 3H]2-DOG uptakes, activations of PI 3-kinase and PKCζ 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-PKCζ pathway and downregulates adiposity in OLETF rats. |
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Keywords: | Dehydroepiandrosterone Adipocytes Insulin sensitivity OLETF rats PDK1 PKCζ |
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