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

• Published in: Diabetes (New York, N.Y.) Vol. 61; no. 4; pp. 888 - 896
• Main Authors: Chai, Weidong, Dong, Zhenhua, Wang, Nasui, Wang, Wenhui, Tao, Lijian, Cao, Wenhong, Liu, Zhenqi
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.2012
• Subjects: Animals; Aorta - cytology; Biological and medical sciences; Blood glucose; Blood sugar; Cardiovascular disease; Cattle; Cells, Cultured; Cyclic AMP-Dependent Protein Kinases - genetics; Cyclic AMP-Dependent Protein Kinases - metabolism; Diabetes; Diabetes. Impaired glucose tolerance; Drug Administration Schedule; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial Cells - metabolism; Endothelium; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Flow velocity; Gene Expression Regulation - physiology; Glucagon; Glucagon-Like Peptide 1 - genetics; Glucagon-Like Peptide 1 - metabolism; Glucagon-Like Peptide 1 - pharmacology; Glucose; Glucose - metabolism; Hormones - pharmacology; Insulin; Insulin - metabolism; Kinases; Laboratories; Male; Medical sciences; Microcirculation; Microvessels; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Muscles; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - blood; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Pathophysiology; Peptide hormones; Peptides; Physiological aspects; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Pulmonary arteries; Rats; Rats, Sprague-Dawley; Somatostatin - pharmacology; Endocrinopathy; Microcirculation; Gastrointestinal hormone; Diabetes mellitus; Nitric oxide; Muscle; Glucose; Glucagon like peptide 1
• DOI: 10.2337/db11-1073
• ISSN: 0012-1797; 1939-327X

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.