Glucagon-like Peptide 1 Increases Muscle Microvascular Recruitment And Glucose Uptake Via A Nitric Oxide-dependent Mechanism

Objective:In addition to its effect on glucose-mediated insulin secretion, glucagon-like peptide 1 (GLP-1) increases tissue glucose uptake and causes vasodilation independent of insulin. The current study examined whether GLP-1 exerts vasodilatory effect on microvasculature and subsequently affects glucose uptake in muscle.Methods:1. Incubation of BAECs with GLp-1 at different doses, Protein kinase B/Akt and endothelial nitric oxide synthase (eNOS) phosphorylation were measured by Western Blot.2. Overnight fasted adult male rats were received continuous GLP-1 infusion (30 pmol/kg/min) for 2 hrs with or without superimposed infusion of NOS inhibitor L-NAME for 30min. Muscle microvascular blood volume (MBV), microvascular blood flow velocity (MFV) and microvascular blood flow (MBF)were determined. Blood samples were collected to measure glucose, insulin and Nitric Oxide level.Results:GLP-1 infusion acutely increased muscle MBV (p<0.04) within 30 min without altering MFV, blood pressure or femoral artery blood flow. This effect persisted throughout the 120 min infusion period, leading to a>2-fold increase in muscle MBF (p<0.02). These changes were paralleled with increases in plasma NO levels (～2-fold, p<0.04), and hindleg glucose extraction (>2-fold, p<0.05). infusion of L-NAME blocked GLP-1-mediated increases in muscle MBV, glucose disposal and NO production.Conclusions:GLP-1 acutely increases microvascular recruitment and basal glucose uptake in muscle via a NO-dependent mechanism. Thus, GLP-1 may afford potential to improve muscle insulin sensitivity and decrease the cardiovascular complications associated with diabetes by expanding microvascular endothelial surface area.