1,25‐Dihydroxyvitamin D improved the free fatty‐acid‐induced insulin resistance in cultured C2C12 cells

Abstract

Background Epidemiological evidence has indicated that vitamin D deficiency increased the risk of insulin resistance in metabolic syndrome. The present study was conducted to test the hypothesis that 1,25‐dihydroxyvitamin D may improve the free fatty‐acid (FFA)‐induced insulin resistance in muscle cells. Method The insulin resistance of muscle cell model was established by treatment of FFA in differentiated C2C12 cells. Glucose uptake of C2C12 myotubes was analysed by the 3H‐labelled 2‐deoxyglucose uptake assay. The diameter of myotubes was measured under the condition of glutaraldehyde‐induced autofluorescense. Tyrosine phosphorylated insulin receptor substrate 1 (IRS‐1) was measured by immunoprecipitation. Serine phosphorylated IRS‐1 and protein kinase B (Akt), extracellular signal‐related kinase (ERK), c‐Jun amino‐terminal kinases (JNK) as well as their phosphorylated form were analysed by Western blots. Results Compared with a vehicle‐treated group, FFA treatment in myotubes was associated with 70.6% reduction in insulin‐mediated uptake of glucose, a five‐fold increase in serine phosphorylation of IRS‐1, 76.9% decrease in tyrosine phosphorylation of IRS‐1 and 81.8% decrease in phosphorylation of Akt. Supplement of 1,25‐dihydroxyvitamin D improved the FFA‐induced inhibition of glucose uptake in a dose‐ dependent (p < 0.001) and time‐dependent manner (p < 0.01). This was accompanied by increase in tyrosine phosphorylation of IRS‐1 and phosphorylated Akt and decrease in serine phosphorylation of IRS‐1 (p < 0.001). 1,25‐Dihydroxyvitamin D also inhibited the FFA‐induced reduction in myotube diameter by 35.3% (p < 0.001). JNK phosphorylation was reduced by 126.7% with treatment of 1,25‐dihydroxyvitamin D (p < 0.001). 1,25‐Dihydroxyvitamin D had no effect on FFA‐induced ERK phosphorylation (p = 0.84). Conclusion 1,25‐Dihydroxyvitamin D improved the FFA‐induced insulin resistance in muscle cells. Copyright © 2008 John Wiley & Sons, Ltd.