Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine

Vitamin D deficiency will lead to insulin resistance. In the current study, vitamin D3 1α-Hydroxylase ["1α(OH)ase"] knockout mice were generated to mimic vitamin D deficiency in vivo. As compared to the wild-type mice, the liver tissues of the knockout mice showed impaired insulin signaling, decreased glucose transporter 4 expression and increased reactive oxygen species production. Meanwhile, p53-p21 activation, apoptosis intensity and pro-inflammatory cytokines (IL-6, IL-1 and MIP-1α) level were significantly increased in the knockout mice livers. Significantly, such effects in the knockout mice were largely attenuated by supplement with anti-oxidant n-acetylcysteine (NAC). Remarkably, insulin resistance and metabolic abnormalities in the knockout mice were largely alleviated after treatment of NAC. Therefore, inhibition of oxidative stress by NAC alleviated insulin resistance in vitamin D-deficient mice. Oxidative stress could be the primary cause of insulin resistance by vitamin D deficiency.