Impact of exercise on vascular and metabolic function across prediabetes and diabetes - over the past decade type 2 diabetes (T2D) have reached epidemic levels in developed countries, becoming one…

The National Institute of General Medical Sciences awarded the University of The Pacific $122,065 on August 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to investigate the effects of moderate and high intensity interval exercise on vascular and metabolic function across prediabetes and diabetes.

The research examines how different exercise intensities affect aortic and mesenteric arterial reactivity and metabolic outcomes in UC Davis type 2 diabetes mellitus rats of both sexes. The project tests the hypothesis that moderate and high intensity interval exercise confer vascular and metabolic benefits with effects dependent on sex and diabetes status, with greater benefits in males during prediabetes and in females during diabetes. Work is structured across two integrated aims: determining the impact of exercise on arterial reactivity across prediabetes and diabetes stages, and investigating mechanisms through which exercise enhances endothelium-dependent vasorelaxation by modulating endothelin-1 signaling and nitric oxide synthase phosphorylation.

Performance occurs in Stockton, California. The period of performance runs from August 1, 2026, through March 31, 2030. The award is classified as a Project Grant.

Impact of exercise on vascular and metabolic function across prediabetes and diabetes - over the past decade type 2 diabetes (T2D) have reached epidemic levels in developed countries, becoming one of the most challenging health problems in the 21ST century. Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in diabetic patients. Several reports including our previous studies suggest that diabetes affect male and female vascular beds differently. We recently demonstrated that the development of vascular and metabolic dysfunction in UC davis type 2 diabetes mellitus (UCD-T2DM) rats is both diabetic state- and SEX-dependent. Regular aerobic exercise is a well-known therapeutic intervention for endothelial dysfunction and CVD risk in T2D. The effects of exercise on adipose tissue (at) distribution and function are also identified. However, there is still debate about the potential benefits of different exercise intensities against deleterious vascular and metabolic consequences, and their underlying mechanisms across prediabetes and diabetes. The objective of this sure application is to investigate the effects of moderate and high intensity interval exercise (MIE and hiie) on aortic and mesenteric arterial and metabolic functions across prediabetes and diabetes in rats of both sexes. This application will test the central hypothesis that the MIE and hiie confer vascular and metabolic benefits, with effects dependent on SEX and diabetes status-greater in males during prediabetes and in females during diabetes. This will be addressed in 2 integrated aims in a relevant model of disease (UCD-T2DM RAT). Aim 1. Determine the impact of MIE and hiie on aortic and mesenteric arterial reactivity across prediabetes and diabetes in rats of both sexes. Hypothesis: MIE and hiie enhance endothelium-dependent vasorelaxation by reducing ET-1 signaling and increasing PI3K-AKT-mediated phosphorylation of endothelial no synthase (p-enos), thereby improving no bioavailability, with effects dependent on SEX and diabetes status. Aim 2. Determine the impact of MIE and hiie on adipose tissue metabolic signaling across prediabetes and diabetes in rats of both sexes. Hypothesis: MIE and hiie improve adipose metabolic function by reducing proinflammatory mediators, enhancing anti-inflammatory signaling, and upregulating genes involved in glucose uptake and oxidation, and DE novo lipogenesis, with effects dependent on SEX and diabetes status. Overall aim: to create significant opportunities for training of undergraduate/ graduate students in high-quality research in vascular biology and metabolic syndrome at pacific.