Vitamin D protects diabetic rats from neuropathic changes by improving insulin sensitivity and upregulating vitamin D receptors

Abstract

Background There is emerging evidence of neuroprotective roles for vitamin D. However, its role in the pathogenesis of type 2 diabetes mellitus (T2DM) and its exact mechanism of action in neuroprotection are still unclear. The present work was designed to examine the effect of vitamin D supplementation on insulin sensitivity and nerve conduction velocity with and without insulin treatment in a diabetic model. Materials and methods This study was carried out on 50 male adult rats. They were divided into five groups: a control group, a diabetic group, in which T2DM was induced; a diabetic insulin-treated group, in which diabetic rats were treated with insulin alone; a diabetic vitamin D-treated group, in which diabetic rats were treated with vitamin D alone; and finally, a diabetic with combined insulin and vitamin D treatment group. At the end of the experimental period, blood samples were obtained from all animals for measurement of serum glucose and insulin, together with the oxidative stress marker malondialdehyde (MDA) and inflammatory markers interleukins 1β and 10 (IL1β and IL10). Nerve conduction velocity was performed on a dissected sciatic nerve. In addition, vitamin D receptor (VDR) gene expressions in pancreatic (VDR-P) and sciatic nerve (VDR-N) tissues were estimated and the homeostasis model assessment for insulin resistance index was calculated for each group. Results Data showed a significant reduction in nerve conduction velocity of the sciatic nerve, together with increased insulin resistance in diabetic rats that paralleled increased MDA and IL1β and decreased IL10. Administration of insulin alone, vitamin D alone, or both combined after induction of diabetes improved the nerve conduction velocity. This improvement was accompanied by significant enhancement of VDR-P and VDR-N gene expression, together with reduction in oxidative stress and inflammatory state. Conclusion The improvement of insulin sensitivity and neuroprotection with vitamin D supplementation in T2DM is related to restoration of VDR-P and VDR-N expression. Thus, vitamin D could be a novel approach to lower neuropathic risk in diabetes.