Diet high in lipid hydroperoxide by vitamin E deficiency induces insulin resistance and impaired insulin secretion in normal rats

Abstract

To clarify the effect of dietary lipid hydroperoxide (LPO) on development of glucose intolerance, we fed Sprague–Dawley rats on a diet containing elevated LPO level for 10 weeks and measured both insulin sensitivity and insulin secretion. The contents of LPO in both plasma and skeletal muscle in the LPO-fed rats were significantly higher than those in the controls. Both insulin resistance evaluated by steady-state blood glucose (SSBG) methods and impaired insulin secretion evaluated by oral glucose tolerance test (OGTT) were found in the LPO-fed rats as compared with control rats. Furthermore, the levels of insulin receptor substrate (IRS)-1 protein in the skeletal muscle were significantly lower in the LPO-fed rats. Those impairments were not reversed in LPO-fed rats with supernormal levels of plasma vitamin E following vitamin E supplementation for 5 weeks. Moreover, the immunohistochemical study revealed that NF-κB-p50 protein was found in the nucleus of pancreatic β-cells of the LPO-fed rats, whereas it was not observed in the nucleus of the islets in the control rats. These findings indicate that NF-κB is activated in response to oxidative stress in pancreatic islet cells in LPO-fed rats. In conclusion, our studies reveal that diet high in LPO by vitamin E deficiency accelerates glucose intolerance through impairments of both sensitivity and secretion of insulin.