title: 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.
authors: Department of Pediatrics, Osaka Medical College.
authors: Kimitaka
authors: K
authors: Takitani
authors: Keisuke
authors: K
authors: Inoue
authors: Maki
authors: M
authors: Koh
authors: Hiroshi
authors: H
authors: Miyazaki
authors: Kanta
authors: K
authors: Kishi
authors: Akiko
authors: A
authors: Inoue
authors: Hiroshi
authors: H
authors: Tamai
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D000072470:Cytochrome P450 Family 4; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000139:chemically induced; D004195:Disease Models, Animal; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D024502:alpha-Tocopherol / Q000097:blood*
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; C017763:alpha-tocopherol transfer protein; D013311:Streptozocin; D003577:Cytochrome P-450 Enzyme System; C465260:Cyp3a2 protein, rat; C465348:Cyp4f1 protein, rat; D051544:Cytochrome P-450 CYP3A; D000072470:Cytochrome P450 Family 4; D024502:alpha-Tocopherol