25-Hydroxyvitamin D Increases Insulin-Stimulated Glucose Uptake by Enhancing Adipocyte Differentiation

Vitamin D and its receptor (vitamin D receptor; VDR) regulate calcium homeostasis in mammals. Recently, studies have shown that serum concentrations of 25-hydroxyvitamin D (25VD) are negatively associated with insulin resistance and the incidence of type 2 diabetes. In adipose tissues, glucose transporter 4 (GLUT4) contributes to insulin-stimulated glucose uptake; however, the effect of 25VD on glucose uptake in adipocytes remains unclear. We examined the role of 25VD in glucose uptake and the differentiation of adipose-derived stromal cells. Insulin-stimulated glucose uptake in adipocytes was increased by treatment with 25VD and decreased by VDR knockdown. The expression levels of GLUT4 were upregulated by 25VD treatment. 25VD exposure increased the expression of adipocyte differentiation-related genes including peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding proteins through VDR, thereby enhancing the formation of mature adipocytes. Moreover, 25VD increased the expression levels of 11β-hydroxysteroid dehydrogenase 1 (HSD11B1), which catalyzes the conversion of cortisone to cortisol in a concentration-dependent manner. 25VD-stimulated adipocyte differentiation was suppressed by HSD11B1 knockdown. Cortisone together with 25VD enhanced adipocyte differentiation, whereas synthesized glucocorticoid dexamethasone-induced adipocyte differentiation is not promoted by 25VD. Overall, these results indicate that 25VD stimulates adipocyte differentiation through the induction of HSD11B1 expression, leading to increased insulin-induced glucose uptake in adipocytes.