title: Physical fitness and endothelial function (nitric oxide synthesis) are independent determinants of insulin-stimulated blood flow in normal subjects.
abstract: Insulin induces vasodilation via stimulation of nitric oxide (NO) synthesis. This action of insulin exhibits considerable interindividual variation. We determined whether the response of blood flow to endothelium-dependent vasoactive agents correlates with that to insulin or whether other factors, such as physical fitness, limb muscularity, or vasodilatory capacity, better explain variations in insulin-stimulated blood flow. Direct measurements of the forearm blood flow response to three 2-h sequential doses of insulin (1, 2, and 5 mU/ kg.min), endothelium-dependent (acetylcholine and NG-monomethyl-L-arginine) and endothelium-independent (sodium nitroprusside) vasoactive agents, and ischemia (reactive hyperemic forearm blood flow) were performed in 22 normal subjects (age, 24 +/- 1 yr; body mass index, 22.2 +/- 0.6 kg/m2; maximal aerobic power, 40 +/- 2 mL/kg.min). The highest insulin dose increased blood flow by 111 +/- 17%. The fraction of basal blood flow inhibited by NG-monomethyl-L-arginine (NO synthesis-dependent flow) varied from 6-47%. Maximal aerobic power (r = 0.52; P < 0.02), the percentage of forearm muscle (r = 0.50; P < 0.02), and the NO synthesis-dependent flow (r = 0.42; P < 0.05), but not reactive hyperemic, acetylcholine-stimulated, or sodium nitroprusside-stimulated flow, were significantly correlated with insulin-stimulated (5 mU/kg.min) blood flow. In multiple linear regression analysis, 52% of the variation (multiple R = 0.72; P < 0.001) in insulin-stimulated blood flow was explained by NO synthesis-dependent flow (P < 0.005) and the percentage of forearm muscle (P < 0.005). We conclude that endothelial function (NO synthesis-dependent basal blood flow) and forearm muscularity are independent determinants of insulin-stimulated blood flow.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Utriainen
authors.forename: S
authors.initials: S
authors.lastname: Mäkimattila
authors.forename: A
authors.initials: A
authors.lastname: Virkamäki
authors.forename: H
authors.initials: H
authors.lastname: Lindholm
authors.forename: A
authors.initials: A
authors.lastname: Sovijärvi
authors.forename: H
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: D000328:Adult; D004730:Endothelium, Vascular / Q000502:physiology*; D005121:Extremities / Q000098:blood supply*; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D010101:Oxygen Consumption; D010809:Physical Fitness; D012039:Regional Blood Flow / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D007328:Insulin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide