title: Glucagon-like peptide 1 recruits microvasculature and increases glucose use in muscle via a nitric oxide-dependent mechanism.
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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA. zl3e@virginia.edu
authors.forename: Weidong
authors.initials: W
authors.lastname: Chai
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Dong
authors.forename: Nasui
authors.initials: N
authors.lastname: Wang
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wang
authors.forename: Lijian
authors.initials: L
authors.lastname: Tao
authors.forename: Wenhong
authors.initials: W
authors.lastname: Cao
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D004334:Drug Administration Schedule; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D008297:Male; D055806:Microvessels; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000494:pharmacology
chemical_list: D006728:Hormones; D007328:Insulin; D009569:Nitric Oxide; D013004:Somatostatin; D052216:Glucagon-Like Peptide 1; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester