title: Supplementation of alpha-tocopherol improves cardiovascular risk factors via the insulin signalling pathway and reduction of mitochondrial reactive oxygen species in type II diabetic rats.
abstract: This study determined the effects of alpha- and gamma-tocopherol supplementation on metabolic control and oxidative stress in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Blood glucose, haemoglobin A1c (HbA1c), urinary protein, plasma free fatty acid, triacylglycerol and plasminogen activator inhibitor-1 (PAI-1) levels in OLETF rats were significantly higher than in non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats. Alpha-tocopherol inhibited the increase in urinary protein, blood glucose, HbA1c and PAI-1 levels, but gamma-tocopherol did not. Plasma and hepatic lipid peroxidation and hepatic steatosis were increased in OLETF rats. alpha-Tocopherol decreased lipid peroxidation. Mitochondrial reactive oxygen species production and uncoupling protein 2 (UCP2) expression were significantly increased in the heart and aorta of OLETF rats compared with LETO rats. Endothelial NO synthase and aortic nitrotyrosine were increased in OLETF rats. In contrast, the expression of phosphorylated vasodilator-stimulated phosphoprotein and glucose transporter 4 in the aorta was significantly decreased in OLETF rats. These abnormalities were reversed by alpha-tocopherol. These findings suggest that alpha-tocopherol may prevent cardiovascular tissues from oxidative stress and insulin signalling disorder resulting from diabetes mellitus.
authors.affiliation: Department of Anti-Aging Food Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho, Okayama, Japan. yukiko-m@md.okayama-u.ac.jp
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Minamiyama
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Takemura
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Bito
authors.forename: Hiroji
authors.initials: H
authors.lastname: Shinkawa
authors.forename: Takuma
authors.initials: T
authors.lastname: Tsukioka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakahira
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Suehiro
authors.forename: Shigeru
authors.initials: S
authors.lastname: Okada
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D002318:Cardiovascular Diseases / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species; D012307:Risk Factors; D015398:Signal Transduction; D024502:alpha-Tocopherol / Q000378:metabolism* / Q000494:pharmacology; D024504:gamma-Tocopherol / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007328:Insulin; D017382:Reactive Oxygen Species; D024504:gamma-Tocopherol; D024502:alpha-Tocopherol