Exercise training enhanced myocardial endothelial nitric oxide synthase (eNOS) function in diabetic Goto-Kakizaki (GK) rats.
Different mechanisms of diabetic-induced NO dysfunction have been proposed and central to most of them are significant changes in eNOS function as the rate-limiting step in NO bioavailability. eNOS exists in both monomeric and dimeric conformations, with the dimeric form catalyzes the rate-limiting step in the synthesis of nitric oxide, while the monomeric form catalyzes the synthesis of superoxide (O2).
Diabetic-induced shifts to decrease the dimer:monomer ratio contributes to the degradation of nitric oxide (NO) bioavailability. Exercise has long been useful in the management of diabetes.
Although exercise-induced increased expression of eNOS has been reported, it is unclear if exercise may alter the functional coupling of eNOS.
Methods: To investigate this question, Goto-Kakizaki rats (a model of type II diabetes) were randomly assigned to a 9-week running program (train) or sedentary (sed) groups.
Results: Exercise training significantly (p<.05) increased plantaris muscle cytochrome oxidase, significantly improved glycosylated hemoglobin (sed: 7.33+/-0.56%; train: 6.1+/-0.18%), as well as insulin sensitivity. Exercise increased both total eNOS expression and the dimer:monomer ratio in the left ventricle LV (sed: 11.7+/-3.2%; train: 41.4+/-4.7%).
Functional analysis of eNOS indicated that exercise induced significant increases in nitric oxide (+28%) production and concomitant decrease in eNOS-dependent superoxide (-12%) production when assayed in the absence of BH4, but not in the presence of exogenous BH4. Exercise training also significantly decreased NADPH-dependent O2 activity.
Conclusions: Exercise-induced increased eNOS dimerization resulted in an increased coupling of the enzyme to facilitate production of NO at the expense of ROS generation, a shift that could serve to decrease diabetic-related oxidative stress and that may serve to lessen diabetic-related complications.
Author: James Grijalva, Steven Hicks, Xiangmin Zhao, Sushma Medikayala, Pawel M. Kaminski, Michael S. Wolin and John G. Edwards
Credits/Source: Cardiovascular Diabetology 2008, 7:34
Published on: 2008-11-19
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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