Glucagon-Like Peptide 1 Recruits Microvasculature and Increases Glucose Use in Muscle via a Nitric Oxide–Dependent Mechanism

  1. Zhenqi Liu1
  1. 1Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia
  2. 2Department of Medicine, Shandong University Jinan Central Hospital, Shandong, People’s Republic of China
  3. 3Department of Medicine, Central South University Xiangya Hospital, Hunan, People’s Republic of China
  4. 4Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina
  1. Corresponding author: Zhenqi Liu, zl3e{at}virginia.edu.

Abstract

Glucagon-like peptide 1 (GLP-1) increases tissue glucose uptake and causes vasodilation independent of insulin. We examined the effect of GLP-1 on muscle microvasculature and glucose uptake. After confirming that GLP-1 potently stimulates nitric oxide (NO) synthase (NOS) phosphorylation in endothelial cells, overnight-fasted adult male rats received continuous GLP-1 infusion (30 pmol/kg/min) for 2 h plus or minus NOS inhibition. Muscle microvascular blood volume (MBV), microvascular blood flow velocity (MFV), and microvascular blood flow (MBF) were determined. Additional rats received GLP-1 or saline for 30 min and muscle insulin clearance/uptake was determined. GLP-1 infusion acutely increased muscle MBV (P < 0.04) within 30 min without altering MFV or femoral blood flow. This effect persisted throughout the 120-min infusion period, leading to a greater than twofold increase in muscle MBF (P < 0.02). These changes were paralleled with increases in plasma NO levels, muscle interstitial oxygen saturation, hind leg glucose extraction, and muscle insulin clearance/uptake. NOS inhibition blocked GLP-1–mediated increases in muscle MBV, glucose disposal, NO production, and muscle insulin clearance/uptake. In conclusion, GLP-1 acutely recruits microvasculature and increases basal glucose uptake in muscle via a NO-dependent mechanism. Thus, GLP-1 may afford potential to improve muscle insulin action by expanding microvascular endothelial surface area.

  • Received August 1, 2011.
  • Accepted December 20, 2011.

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