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Original

Supplementation of α-tocopherol improves cardiovascular risk factors via the insulin signalling pathway and reduction of mitochondrial reactive oxygen species in type II diabetic rats

, PhD, , , , , , & show all
Pages 261-271 | Received 03 Sep 2007, Published online: 07 Jul 2009
 

Abstract

This study determined the effects of α- and γ-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. α-Tocopherol inhibited the increase in urinary protein, blood glucose, HbA1c and PAI-1 levels, but γ-tocopherol did not. Plasma and hepatic lipid peroxidation and hepatic steatosis were increased in OLETF rats. α-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 α-tocopherol. These findings suggest that α-tocopherol may prevent cardiovascular tissues from oxidative stress and insulin signalling disorder resulting from diabetes mellitus.

Abbreviations
COX=

cytochrome oxidase

eNOS=

endothelial NO synthase

FFA=

free fatty acid

GLUT=

glucose transporter

LETO=

Long-Evans Tokushima Otsuka

OLETF=

Otsuka-Long Evans Tokushima Fatty

pVASP=

phosphorylated vasodilator-stimulated phosphoprotein

PAI-1=

plasminogen activator inhibitor-1

ROS=

reactive oxygen species

SOD=

superoxide dismutase

UCP2=

Uncoupling protein 2.

Abbreviations
COX=

cytochrome oxidase

eNOS=

endothelial NO synthase

FFA=

free fatty acid

GLUT=

glucose transporter

LETO=

Long-Evans Tokushima Otsuka

OLETF=

Otsuka-Long Evans Tokushima Fatty

pVASP=

phosphorylated vasodilator-stimulated phosphoprotein

PAI-1=

plasminogen activator inhibitor-1

ROS=

reactive oxygen species

SOD=

superoxide dismutase

UCP2=

Uncoupling protein 2.

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