Effect of vitamin D3in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

Abstract

Diabetes mellitus is a growing health problem worldwide and is associated with severe liver complications. The aim of the present study is to analyse the status of metabolic and free-radical-scavenging enzymes and second messengers in the liver of streptozotocin (STZ)-induced diabetic rats, and to determine the hepatoprotective role of vitamin D3. All studies were performed using the liver of adult male Wistar rats. Gene expression studies were carried out using real-time PCR with specific probes. Second messenger levels were determined using3H-labelled Biotrak assay kits, and glucose uptake assay withd-[14C]glucose. The present results show that there was a decrease in hepatic glucose uptake, malate dehydrogenase activity, glycogen content, inositol triphosphate (IP3) and cyclic GMP levels, and superoxide dismutase, glutathione peroxidase, phospholipase C, cyclic AMP-responsive element-binding protein, vitamin D receptor (VDR) and insulin receptor (INSR) gene expression in the diabetic rats when compared with the controls (allP < 0·05), while cyclic AMP levels and GLUT2 expression were increased (P < 0·05). Treatment of the diabetic rats with vitamin D3and insulin reversed the altered parameters to near control values. In conclusion, the data suggest a novel role of vitamin D3in restoring impaired liver metabolism in STZ-induced diabetic rats by regulating glucose uptake, storage and metabolism. We demonstrated that the restoring effect of vitamin D3is mediated through VDR modulation, thereby improving signal transduction and controlling free radicals in the liver of diabetic rats. These data suggest a potential role for vitamin D3in the treatment of diabetes-associated hepatic complications.