# Effects of Exercise and GLP-1R Agonism on Muscle Microvascular Perfusion and Insulin Action

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $656,830

## Abstract

Project Summary/Abstract
Patients with metabolic syndrome exhibit metabolic insulin resistance, have increased
risks of cardiovascular events and are prone to developing type 2 diabetes mellitus.
Substantial evidence has established the value of high levels of physical activity,
exercise training, and overall cardiorespiratory fitness in the prevention of
cardiovascular diseases. Glucagon-like peptide 1 (GLP-1) receptor agonists have been
shown to reduce the new onset of diabetes in adult humans with prediabetes and the
rate of major adverse cardiovascular events among patients with type 2 diabetes. The
mechanisms underpinning the cardiovascular benefits of exercise and GLP-1 receptor
agonism remain elusive. In the proposed studies, we will test an overarching hypothesis
that exercise and GLP-1 receptor agonism each enhance insulin-mediated
microvascular perfusion and muscle angiogenesis, leading to increased muscle delivery
and action of insulin in the insulin resistant state. We further hypothesize that the
combination of both would be more effective. We will use a translational approach to
examine the effects of exercise and GLP-1 receptor agonism on both skeletal muscle
and coronary microvasculature in humans with metabolic syndrome and the role of
endothelial AMPK and mitochondrial fission in the pathogenesis of microvascular insulin
resistance. We will use a state-of-the-art technique, contrast-enhanced ultrasound, in
combination with arteriovenous balance, muscle biopsy and insulin clamp to quantify
the effects of exercise training and GLP-1 receptor agonism on microvascular and
metabolic responses to insulin in humans with insulin resistance/metabolic syndrome
and open a new avenue for future mechanistic and/or therapeutic studies. We will
further use a variety of rodent models to explore the underlying mechanisms. By
understanding the regulation of skeletal and cardiac muscle microvascular function and
insulin responses in humans with metabolic syndrome, it may be possible to correct
vascular and ameliorate metabolic insulin resistance to prevent diabetes and decrease
the associated cardiovascular risks.

## Key facts

- **NIH application ID:** 10170355
- **Project number:** 5R01DK125330-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** ZHENQI LIU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $656,830
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170355

## Citation

> US National Institutes of Health, RePORTER application 10170355, Effects of Exercise and GLP-1R Agonism on Muscle Microvascular Perfusion and Insulin Action (5R01DK125330-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10170355. Licensed CC0.

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