SPUR 2018 Projects: Health

Physical Therapy & Athletic Training | College of Health

Novel approaches to reduce muscle atrophy and metabolic dysfunction in older adults during physical inactivity
Micah Drummond, Associate Professor

Hospitalizations for disease, injury, and/or surgery in older adults are likely to impair physical mobility and, therefore, the older adults capacity to be physically active both during hospitalization and beyond. The resulting sedentary lifestyle is likely to be accepted as the "new normal", ultimately increasing the risk of skeletal muscle and metabolic dysfunction (e.g. insulin resistance and sarcopenia). Muscle atrophy and insulin resistance are an unfortunate consequence with disuse in older adults. We have observed with our bed rest studies in healthy older adults that in addition to muscle and metabolic changes, we notice increased skeletal muscle inflammation, impaired glucose uptake signaling and an upregulation of enzymes related to de novo ceramide biosynthesis. The accumulation of ceramide, a toxic lipid intermediate, can disrupt glucose homeostasis and impair muscle growth. Insulin sensitizers (common diabetic glucose lowering medications) not only improve insulin sensitivity but may be able to attenuate muscle loss in insulin resistant adults through a mechanism that may involve ceramide synthesis. This might be a useful preventive strategy to maintain muscle and metabolic health during a period of physical inactivity in older adults has not been investigated. Therefore, we have proposed to conduct a clinical study in healthy glucose tolerant older adults to test if specific insulin sensitizers during bed rest will attenuate insulin resistance, muscle loss and accumulation of ceramides. These findings will be foundational in the development of novel treatments to prevent insulin resistance and muscle atrophy in older adults during disuse periods.

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Nutrition & Integrative Physiology | College of Health

Mechanistic insights into the vascular effects of blueberries
Anandh Babu Pon Velayutham, Assistant Professor

The research in our laboratory is focused on the vascular effects of blueberries with special emphasis on circulating metabolites and the molecular signaling mechanisms involved. Diabetes greatly increases the risk of cardiovascular diseases such as atherosclerosis, which accounts for the largest number of deaths among American diabetic patients. High glucose induced vascular inflammation and dysfunction play a major role in the pathogenesis of atherosclerosis in diabetes. The vascular endothelium is covered with glycocalyx which act as an orchestrator of vascular homeostasis. The structure/function of glycocalyx is compromised in the vessels of diabetic patients, which enhances the sensitivity of the vasculature towards inflammatory stimuli leading to cardiovascular disease. Hence, preservation/restoration of glycocalyx structure may be a novel strategy to ameliorate vascular complications in diabetes.  Epidemiological and clinical studies support the vascular effects of anthocyanins - one class of flavonoids widely available in berry fruits. In our study, dietary blueberries ameliorated vascular inflammation/dysfunction in diabetic mice. Further, blueberry metabolites at physiologically relevant concentrations, suppressed high fat and diabetes-induced endothelial inflammation in human aortic endothelial cells (Mol Nutr Food Research 2017). Our current project determines (1) whether dietary blueberry ameliorates vascular complications in diabetes by modulating endothelial glycocalyx, and (2) the role of circulating metabolites in exerting such vascular effects. Understanding and validating the bioactivities of blueberry will provide a solid scientific foundation to recommend blueberries to improve vascular health.

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