title: Insulin Enhances Endothelial Function Throughout the Arterial Tree in Healthy But Not Metabolic Syndrome Subjects.
abstract: BACKGROUND
  Insulin reportedly impairs endothelial function in conduit arteries but improves it in resistance and microvascular arterioles in healthy humans. No studies have assessed endothelial function at three arterial levels in healthy or metabolic syndrome (METSYN) subjects.
  
  
  OBJECTIVE
  The objective of the study was to compare endothelial responsiveness of conduit arteries, resistance, and microvascular arterioles to insulin in healthy and METSYN subjects.
  
  
  METHODS
  We assessed conduit, resistance, and microvascular arterial function in the postabsorptive and postprandial states and during euglycemic hyperinsulinemia (insulin clamp).
  
  
  METHODS
  The study was conducted at a clinical research unit.
  
  
  METHODS
  Age-matched healthy and METSYN subjects participated in the study.
  
  
  METHODS
  We used brachial flow-mediated dilation, forearm postischemic flow velocity, and contrast-enhanced ultrasound to assess the conduit artery, resistance arteriole, and microvascular arteriolar endothelial function, respectively. We also assessed the conduit artery stiffness (pulse wave velocity and augmentation index) and measured the plasma concentrations of 92 cardiovascular disease biomarkers at baseline and after the clamp.
  
  
  RESULTS
  Postabsorptive and postprandial endothelial function was similar in controls and METSYN in all tested vessels. METSYN subjects were metabolically insulin resistant (P < .005). In controls, but not METSYN subjects, during euglycemic hyperinsulinemia, endothelial function improved at each level of arterial vasculature (P < .05 or less for each). Conduit vessel stiffness (pulse wave velocity) was increased in the METSYN group. Twelve of 92 biomarkers differed at baseline (P < .001) and remained different at the end of the insulin clamp.
  
  
  CONCLUSIONS
  We conclude that insulin enhances arterial endothelial function in health but not in METSYN, and this vascular insulin resistance may underlie its increased cardiovascular disease risk.
authors.affiliation: Departments of Medicine (L.A.J., L.H., N.R., B.L., J.J.K., K.A., E.J.B.) and Pharmacology (E.J.B.), University of Virginia School of Medicine, Charlottesville, Virginia 22908; Department of Molecular and Clinical Medicine (L.-M.G., H.U.W.), Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden; and CVMD iMED (L.-M.G.), Department of Research and Development, AstraZeneca, 431 83 Mölndal, Sweden.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Jahn
authors.affiliation: Departments of Medicine (L.A.J., L.H., N.R., B.L., J.J.K., K.A., E.J.B.) and Pharmacology (E.J.B.), University of Virginia School of Medicine, Charlottesville, Virginia 22908; Department of Molecular and Clinical Medicine (L.-M.G., H.U.W.), Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden; and CVMD iMED (L.-M.G.), Department of Research and Development, AstraZeneca, 431 83 Mölndal, Sweden.
authors.forename: Lee
authors.initials: L
authors.lastname: Hartline
authors.affiliation: Departments of Medicine (L.A.J., L.H., N.R., B.L., J.J.K., K.A., E.J.B.) and Pharmacology (E.J.B.), University of Virginia School of Medicine, Charlottesville, Virginia 22908; Department of Molecular and Clinical Medicine (L.-M.G., H.U.W.), Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden; and CVMD iMED (L.-M.G.), Department of Research and Development, AstraZeneca, 431 83 Mölndal, Sweden.
authors.forename: Nagashree
authors.initials: N
authors.lastname: Rao
authors.affiliation: Departments of Medicine (L.A.J., L.H., N.R., B.L., J.J.K., K.A., E.J.B.) and Pharmacology (E.J.B.), University of Virginia School of Medicine, Charlottesville, Virginia 22908; Department of Molecular and Clinical Medicine (L.-M.G., H.U.W.), Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden; and CVMD iMED (L.-M.G.), Department of Research and Development, AstraZeneca, 431 83 Mölndal, Sweden.
authors.forename: Brent
authors.initials: B
authors.lastname: Logan
authors.affiliation: Departments of Medicine (L.A.J., L.H., N.R., B.L., J.J.K., K.A., E.J.B.) and Pharmacology (E.J.B.), University of Virginia School of Medicine, Charlottesville, Virginia 22908; Department of Molecular and Clinical Medicine (L.-M.G., H.U.W.), Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden; and CVMD iMED (L.-M.G.), Department of Research and Development, AstraZeneca, 431 83 Mölndal, Sweden.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Departments of Medicine (L.A.J., L.H., N.R., B.L., J.J.K., K.A., E.J.B.) and Pharmacology (E.J.B.), University of Virginia School of Medicine, Charlottesville, Virginia 22908; Department of Molecular and Clinical Medicine (L.-M.G., H.U.W.), Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden; and CVMD iMED (L.-M.G.), Department of Research and Development, AstraZeneca, 431 83 Mölndal, Sweden.
authors.forename: Kevin
authors.initials: K
authors.lastname: Aylor
authors.affiliation: Departments of Medicine (L.A.J., L.H., N.R., B.L., J.J.K., K.A., E.J.B.) and Pharmacology (E.J.B.), University of Virginia School of Medicine, Charlottesville, Virginia 22908; Department of Molecular and Clinical Medicine (L.-M.G., H.U.W.), Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden; and CVMD iMED (L.-M.G.), Department of Research and Development, AstraZeneca, 431 83 Mölndal, Sweden.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Gan
authors.affiliation: Departments of Medicine (L.A.J., L.H., N.R., B.L., J.J.K., K.A., E.J.B.) and Pharmacology (E.J.B.), University of Virginia School of Medicine, Charlottesville, Virginia 22908; Department of Molecular and Clinical Medicine (L.-M.G., H.U.W.), Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden; and CVMD iMED (L.-M.G.), Department of Research and Development, AstraZeneca, 431 83 Mölndal, Sweden.
authors.forename: Helena U
authors.initials: HU
authors.lastname: Westergren
authors.affiliation: Departments of Medicine (L.A.J., L.H., N.R., B.L., J.J.K., K.A., E.J.B.) and Pharmacology (E.J.B.), University of Virginia School of Medicine, Charlottesville, Virginia 22908; Department of Molecular and Clinical Medicine (L.-M.G., H.U.W.), Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden; and CVMD iMED (L.-M.G.), Department of Research and Development, AstraZeneca, 431 83 Mölndal, Sweden.
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Barrett
mesh_terms: D000328:Adult; D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D015309:Glucose Clamp Technique; D006262:Health; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology*; D008875:Middle Aged; D063177:Pulse Wave Analysis; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D007328:Insulin