Muscle microvasculature critically regulates endothelial exchange surface area to facilitate trans-endothelial delivery of insulin, nutrients and oxygen to myocytes. Insulin resistance blunts insulin-mediated microvascular recruitment and decreases muscle capillary density; both contribute to lower microvascular blood volume. Glucagon-like peptide 1 (GLP-1) and its analogs are able to dilate blood vessels and stimulate endothelial cell proliferation. In this study, we aim to determine the effects of sustained stimulation of the GLP-1 receptors on insulin-mediated capillary recruitment and metabolic insulin responses, small arterial endothelial function and muscle capillary density. Rats were fed a high fat diet (HFD) for 4 weeks with or without simultaneous administration of liraglutide and subject to a euglycemic hyperinsulinemic clamp for 120 min after an overnight fast. Insulin-mediated muscle microvascular recruitment and muscle oxygenation were determined before and during insulin infusion. Muscle capillary density was determined and distal saphenous artery was used for determination of endothelial function and insulin-mediated vasodilation. HFD induced muscle microvascular insulin resistance and small arterial vessel endothelial dysfunction and decreased muscle capillary density. Simultaneous treatment of HFD fed rats with liraglutide prevented all these changes and improved insulin-stimulated glucose disposal. These were associated with a significantly increased AMPK phosphorylation and the expressions of VEGF and its receptors. We conclude that GLP-1 receptor agonists may exert its salutary glycemic effect via improving microvascular insulin sensitivity and muscle capillary density during the development of insulin resistance and early use of GLP-1R agonists may attenuate metabolic insulin resistance as well as prevent cardiovascular complications of diabetes.
- Endothelial function
- insulin resistance
- Glucagon-like peptide 1
- Copyright © 2016, American Journal of Physiology - Endocrinology and Metabolism