α-tocopherol status and altered expression of α-tocopherol-related proteins in streptozotocin-induced type 1 diabetes in rat models

Abstract

Vitamin E plays a critical role as an antioxidant in several pathological conditions, including diabetes, cancer, cardiovascular diseases, and neurodegenerative disorders. Diabetes is a metabolic disorder of glucose due to the lack of adequate insulin production (type 1) or peripheral insulin resistance (type 2). Oxidative stress plays a major role in the pathogenesis of diabetes and its complications. The purpose of the present study was to determine α-tocopherol status and the expression of α-tocopherol-related proteins, including binding proteins and metabolizing enzymes, under streptozotocin (STZ)-induced type 1 diabetes in rat models. In STZ rats, plasma α-tocopherol levels decreased compared to the control rats, whereas hepatic α-tocopherol levels in the STZ rats were significantly increased. CuZn-superoxide dismutase (SOD) gene expression in the liver of STZ rats was markedly decreased, whereas Mn-SOD gene expression remained unaltered. Accelerated lipid peroxidation in the liver of STZ rats was observed and the hepatic expression of α-tocopherol transfer protein (α-TTP) in STZ rats decreased compared to that in the controls. The hepatic expression of cytochrome P450 4F2 (CYP4F2) and CYP3A2 genes in STZ rats also decreased. The reduced expression of hepatic α-TTP and CYP4F2 genes probably leads to decreased plasma α-tocopherol levels and elevated α-tocopherol levels in the liver of STZ rats. The altered expression of hepatic α-tocopherol-related proteins might regulate α-tocopherol status in type 1 diabetes. Determining the mechanism of modulating α-tocopherol status may be helpful in promoting antioxidant therapy in diabetes.