American Diabetes Association
Browse
Supplemental_Material.doc.pdf (526.36 kB)

Liraglutide and Exercise Synergistically Attenuate Vascular Inflammation and Enhance Metabolic Insulin Action in Early Diet-induced Obesity

Download (526.36 kB)
figure
posted on 2023-04-19, 14:58 authored by Jia Liu, Kevin W. Aylor, Zhenqi Liu

  

Inflammation-induced vascular insulin resistance is an early event in diet-induced obesity and contributes to metabolic insulin resistance. To examine whether exercise and glucagon-like peptide 1 (GLP-1) receptor agonism, alone or in combination, modulate vascular and metabolic insulin actions during obesity development, we performed a euglycemic insulin clamp in adult male rats after 2 weeks of high-fat diet feeding with either access to running wheel (exercise), liraglutide, or both. Rats exhibited increased visceral adiposity and blunted microvascular and metabolic insulin responses. Exercise and liraglutide alone each improved muscle insulin sensitivity but their combination fully restored insulin-mediated glucose infusion rates. The combined exercise and liraglutide intervention enhanced insulin-mediated muscle microvascular perfusion, reduced perivascular macrophage accumulation and superoxide production in the muscle, attenuated blood vessel inflammation and improved endothelial function, along with increased endothelial nucleus translocation of NRF2 and increased endothelial AMPK phosphorylation. We conclude that exercise and liraglutide synergistically enhance the metabolic actions of insulin and reduce vascular oxidative stress and inflammation in the early stage of obesity development. Our data suggest that early combination use of exercise and GLP-1 receptor agonism might be an effective strategy in preventing vascular and metabolic insulin resistance and associated complications during the development of obesity.

Funding

This work was supported by National Institutes of Health Grants R01DK125330 and R01DK1124344 (to Z.L.).

History

Usage metrics

    Diabetes

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC