title: GLP-1 at physiological concentrations recruits skeletal and cardiac muscle microvasculature in healthy humans.
abstract: Muscle microvascular surface area determines substrate and hormonal exchanges between plasma and muscle interstitium. GLP-1 (glucagon-like peptide-1) regulates glucose-dependent insulin secretion and has numerous extrapancreatic effects, including a salutary vascular action. To examine whether GLP-1 recruits skeletal and cardiac muscle microvasculature in healthy humans, 26 overnight-fasted healthy adults received a systemic infusion of GLP-1 (1.2 pmol/kg of body mass per min) for 150 min. Skeletal and cardiac muscle MBV (microvascular blood volume), MFV (microvascular flow velocity) and MBF (microvascular blood flow) were determined at baseline and after 30 and 150 min. Brachial artery diameter and mean flow velocity were measured and total blood flow was calculated before and at the end of the GLP-1 infusion. GLP-1 infusion raised plasma GLP-1 concentrations to the postprandial levels and suppressed plasma glucagon concentrations with a transient increase in plasma insulin concentrations. Skeletal and cardiac muscle MBV and MBF increased significantly at both 30 and 150 min (P<0.05). MFV did not change in skeletal muscle, but decreased slightly in cardiac muscle. GLP-1 infusion significantly increased brachial artery diameter (P<0.005) and flow velocity (P=0.05) at 150 min, resulting in a significant increase in total brachial artery blood flow (P<0.005). We conclude that acute GLP-1 infusion significantly recruits skeletal and cardiac muscle microvasculature in addition to relaxing the conduit artery in healthy humans. This could contribute to increased tissue oxygen, nutrient and insulin delivery and exchange and therefore better prandial glycaemic control and tissue function in humans.
authors.affiliation: *Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
authors.forename: Sharmila C
authors.initials: SC
authors.lastname: Subaran
authors.affiliation: *Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Sauder
authors.affiliation: *Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
authors.forename: Weidong
authors.initials: W
authors.lastname: Chai
authors.affiliation: *Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Jahn
authors.affiliation: †Division of Cardiovascular Medicine, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
authors.forename: Dale E
authors.initials: DE
authors.lastname: Fowler
authors.affiliation: *Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Aylor
authors.affiliation: ‡Division of Endocrinology and Metabolism, Department of Medicine, Mayo Clinic, Rochester, MN 55905, U.S.A.
authors.forename: Ananda
authors.initials: A
authors.lastname: Basu
authors.affiliation: *Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D054795:Incretins / Q000494:pharmacology*; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D054795:Incretins; D052216:Glucagon-Like Peptide 1; D005934:Glucagon