1α,25-Dihydroxy vitamin D3によるインスリン抵抗性発現機構

概要

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1α, 25-Dihydroxy vitamin D 3 (1, 25D 3 ) activates conventional PKC and may subsequently cause insulin resistance. Against this background, we examined the effect of 1, 25D 3 on PKC β and PKCζ/λ activities in vitro and insulin-induced glucose uptake in rat adipocytes. A 1, 25D 3 dose-responsively activated PKCβ activity in an immunoprecipitate with anti-PKCβ antibody (ED 50%, 10 nM), but not PKCζ/λ activity. Pretreatment with 1, 25D 3 dose-responsively suppressed insulin-induced glucose uptake. 1, 25D 3 increased membrane-associated PKCβ immunoreactivity. Preincubation with 1, 25D 3 repressed insulin-induced phosphatidylinositol 3 -kinase activation. To assess the PKCβ-mediated inhibition of insulin-induced glucose uptake, preincubation with either Go6976 or LY379196, conventional PKC inhibitors, abolished 1, 25D 3 -mediated inhibitory effect on insulin-induced 2 -deoxyglucose (DOG) uptake. Moreover, the inhibitory effect of 1, 25D 3 on insulin-induced DOG uptake was abrogated in adipocytes overexpressed with dominant negative PKCβII, but not in those overexpressed with wild type PKCβ. These results suggest that 1, 25D 3 reduces insulin-induced glucose uptake via activation of PKCβ in rat adipocytes.
岐阜大学の論文
2003-03-31