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Diabetologia

Erschienen in:

01.07.2008 | Article

Exercise restores endothelial function independently of weight loss or hyperglycaemic status in db/db mice

verfasst von: F. Moien-Afshari, S. Ghosh, M. Khazaei, T. J. Kieffer, R. W. Brownsey, I. Laher

Erschienen in: Diabetologia | Ausgabe 7/2008

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Abstract

Aims/hypothesis

Exercise ameliorates oxidative stress-mediated diabetic vascular endothelial dysfunction through poorly defined mechanisms. We hypothesised that, in addition to improving metabolic parameters, upregulation of antioxidants such as superoxide dismutase (SOD) mediates exercise-induced reductions of oxidative stress and increased nitric oxide (NO) bioavailability, and also restores vasodilatation.

Methods

Type 2 diabetic db/db and normoglycaemic wild-type mice were exercised at moderate intensity for 1 h a day for 7 weeks, leading to a 10% body weight loss. Sedentary animals or those undergoing a low-intensity exercise regimen causing non-significant weight loss were also used. We examined aortic endothelial cell function, NO bioavailability and various biomarkers of oxidative stress.

Results

Moderate-intensity exercise lowered body weight, increased mitochondrial manganese SOD (MnSOD) and both total and phosphorylated (Ser1177) endothelial nitric oxide synthase (eNOS) protein production; it also reduced whole-body (plasma 8-isoprostane) and tissue oxidative stress (nitrotyrosine immunostaining or protein carbonyl levels in the aorta). Low-intensity exercise did not alter body weight; however, it upregulated cytosolic Cu/Zn-SOD instead of MnSOD, and still demonstrated all the above benefits in the db/db aorta. Importantly, both exercise protocols improved endothelial-dependent vasodilatation and NO bioavailability without altering hyperglycaemic status in db/db mice.

Conclusions/interpretation

Exercise reverses diabetic vascular endothelial dysfunction independently of improvements in body weight or hyperglycaemia. Our data suggest that upregulation of eNOS and specific SOD isoforms could play important roles in improving NO bioavailability, as well as in reversing endothelial dysfunction in type 2 diabetes patients through lifestyle modifications in the management of diabetes.

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Titel: Exercise restores endothelial function independently of weight loss or hyperglycaemic status in db/db mice
verfasst von: F. Moien-Afshari
S. Ghosh
M. Khazaei
T. J. Kieffer
R. W. Brownsey
I. Laher
Publikationsdatum: 01.07.2008
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 7/2008
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-008-0996-x

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