Enhancing Exercise's Benefits Protected Against Diabetic Cardiomyopathy

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In a new study, researchers managed to magnify the benefit of exercise so that it provided significant protection from diabetic cardiomyopathy.

“This is a proof of concept. It shows that an antioxidant coming from skeletal muscle that can be induced by exercise training can provide profound protection against an important detrimental disease condition,” study researcher Zhen Yan, PhD, of the University of Virginia School of Medicine, said in a press release. 

“The implication is if we can come up with a strategy to promote [this effect] in people who are vulnerable to, or already developing, diabetes, that could prevent the development of diabetic cardiomyopathy.”

In genetically modified mice, Dr. Yan and colleagues demonstrated that enhancing production of the molecule extracellular superoxide dismutase (EcSOD) — which is produced in skeletal muscle and promoted by regular exercise — would prevent the damaging effects of diabetic cardiomyopathy.

Although this study amplified the expression of EcSOD to levels beyond those achieved with normal exercise, Dr. Yan noted that the findings underscore the benefits of regular exercise in general.

In those who cannot exercise, however, a shortage of the molecule could exacerbate health problems.

“It’s quite possible that there could be a vicious cycle of inactivity. Conditions like heart failure or other chronic diseases would lead to loss of physical capacity and fitness and reduced activity, and due to the difficulties of exercising, this would lead to reduced expression of EcSOD, make them more vulnerable and accelerate their disease process,” Dr. Yan said. 

“So that is one of the reasons I personally believe that exercise is such a powerful intervention. It’s not only that exercise itself is really powerful, there’s a secondary consequence of inactivity.”

Dr. Yan said he aims to identify ways to stimulate production of EcSOD using a drug, or what one might call an exercise pill, to help those who are unable to participate in physical activity. Although this goal is far in the future, this study's findings represent encouraging first steps.

“For this particular study, we wanted to know precisely what is the contribution of muscle-derived EcSOD,” he said. “With that understanding, we can design experimental and clinical interventions to help patients. So that’s our next step.”

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Enhancing Exercise's Benefits Protected Against Diabetic Cardiomyopathy

Background

Exercise training enhances extracellular superoxide dismutase (EcSOD) expression in skeletal muscle and elicits positive health outcomes in individuals with diabetes mellitus. The goal of this study was to determine if enhanced skeletal muscle expression of EcSOD is sufficient to mitigate streptozotocin-induced diabetic cardiomyopathy.

Methods and Results

Exercise training promotes EcSOD expression in skeletal muscle and provides protection against diabetic cardiomyopathy; however, it is not known if enhanced expression of EcSOD in skeletal muscle plays a functional role in this protection. Here, we show that skeletal muscle–specific EcSOD transgenic mice are protected from cardiac hypertrophy, fibrosis, and dysfunction under the condition of type 1 diabetes mellitus induced by streptozotocin injection.

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