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Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2011 Aug; Vol. 301 (2), pp. H306-14. Date of Electronic Publication: 2011 May 20. - Publication Year :
- 2011
-
Abstract
- Type 2 diabetes (T2D) is a leading risk factor for a variety of cardiovascular diseases including coronary heart disease and atherosclerosis. Exercise training (ET) has a beneficial effect on these disorders, but the basis for this effect is not fully understood. This study was designed to investigate whether the ET abates endothelial dysfunction in the aorta in T2D. Heterozygous controls (m Lepr(db)) and type 2 diabetic mice (db/db; Lepr(db)) were either exercise entrained by forced treadmill exercise or remained sedentary for 10 wk. Ex vivo functional assessment of aortic rings showed that ET restored acetylcholine-induced endothelial-dependent vasodilation of diabetic mice. Although the protein expression of endothelial nitric oxide synthase did not increase, ET reduced both IFN-γ and superoxide production by inhibiting gp91(phox) protein levels. In addition, ET increased the expression of adiponectin (APN) and the antioxidant enzyme, SOD-1. To investigate whether these beneficial effects of ET are APN dependent, we used adiponectin knockout (APNKO) mice. Indeed, impaired endothelial-dependent vasodilation occurred in APNKO mice, suggesting that APN plays a central role in prevention of endothelial dysfunction. APNKO mice also showed increased protein expression of IFN-γ, gp91(phox), and nitrotyrosine but protein expression of SOD-1 and -3 were comparable between wild-type and APNKO. These findings in the aorta imply that APN suppresses inflammation and oxidative stress in the aorta, but not SOD-1 and -3. Thus ET improves endothelial function in the aorta in T2D via both APN-dependent and independent pathways. This improvement is due to the effects of ET in inhibiting inflammation and oxidative stress (APN-dependent) as well as in improving antioxidant enzyme (APN-independent) performance in T2D.
- Subjects :
- Adiponectin blood
Adiponectin genetics
Adiponectin metabolism
Analysis of Variance
Animals
Aorta drug effects
Aorta physiopathology
Diabetes Mellitus, Type 2 genetics
Diabetes Mellitus, Type 2 metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelium, Vascular drug effects
Endothelium, Vascular physiopathology
Inflammation Mediators metabolism
Interferon-gamma metabolism
Male
Membrane Glycoproteins metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
NADPH Oxidase 2
NADPH Oxidases metabolism
Nitric Oxide metabolism
Oxidative Stress
Superoxide Dismutase metabolism
Superoxide Dismutase-1
Superoxides metabolism
Time Factors
Tyrosine analogs & derivatives
Tyrosine metabolism
Vasodilator Agents pharmacology
Aorta metabolism
Diabetes Mellitus, Type 2 physiopathology
Endothelium, Vascular metabolism
Physical Exertion
Signal Transduction drug effects
Vasodilation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 301
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 21602470
- Full Text :
- https://doi.org/10.1152/ajpheart.01306.2010