GLP-1 and Insulin Recruit Muscle Microvasculature and Dilate Conduit Artery Individually But Not Additively in Healthy Humans.

contextGlucagon-like peptide-1 (GLP-1) and insulin increase muscle microvascular perfusion, thereby increasing tissue endothelial surface area and nutrient delivery.

objectiveTo examine whether GLP-1 and insulin act additively on skeletal and cardiac microvasculature and conduit artery.

designHealthy adults underwent three study protocols in random order.

settingClinical Research Unit at the University of Virginia.

methodsOvernight-fasted participants received an intravenous infusion of GLP-1 (1.2 pmol/kg/min) or normal saline for 150 minutes with or without a 2-hour euglycemic insulin clamp (1 mU/kg/min) superimposed from 30 minutes onward. Skeletal and cardiac muscle microvascular blood volume (MBV), flow velocity, and flow; brachial artery diameter, flow velocity, and blood flow; and pulse wave velocity (PWV) were measured.

resultsGLP-1 significantly increased skeletal and cardiac muscle MBV and microvascular blood flow (MBF) after 30 minutes; these remained elevated at 150 minutes. Insulin also increased skeletal and cardiac muscle MBV and MBF. Addition of insulin to GLP-1 did not further increase skeletal and cardiac muscle MBV and MBF. GLP-1 and insulin increased brachial artery diameter and blood flow, but this effect was not additive. Neither GLP-1, insulin, nor GLP-1 and insulin altered PWV. Combined GLP-1 and insulin infusion did not result in higher whole-body glucose disposal.

conclusionGLP-1 and insulin at physiological concentrations acutely increase skeletal and cardiac muscle microvascular perfusion and dilate conduit artery in healthy adults; these effects are not additive. Thus, GLP-1 and insulin may regulate skeletal and cardiac muscle endothelial surface area and nutrient delivery under physiological conditions.