title: The interaction of blood flow, insulin, and bradykinin in regulating glucose uptake in lower-body adipose tissue in lean and obese subjects.
abstract: BACKGROUND
  Impaired adipose tissue (AT) blood flow has been implicated in the pathogenesis of insulin resistance in obesity. Insulin and bradykinin are meal-stimulated promoters of AT blood flow and glucose metabolism.
  
  
  OBJECTIVE
  We tested whether blood flow regulates glucose metabolism in AT, insulin and bradykinin exert additive effects on AT blood flow and metabolism, and any of these actions explains the insulin resistance observed in obese individuals.
  
  
  METHODS
  Perfusion and glucose metabolism in the AT of the thighs were studied by positron emission tomography and H(2)(15)O (flow tracer) and (18)F-2-fluoro-2-deoxyglucose. Study I included five subjects in whom positron emission tomography imaging was performed in the fasting state during intraarterial infusion of bradykinin in the left leg; the right leg served as a control. Study II included seven lean and eight obese subjects in whom the imaging protocol was performed during euglycemic hyperinsulinemia.
  
  
  RESULTS
  Bradykinin alone doubled fasting AT blood flow without modifying glucose uptake. Hyperinsulinemia increased AT blood flow (P ≤ 0.05) similarly in lean and obese individuals. In the lean group, bradykinin increased insulin-mediated AT glucose uptake from 8.6 ± 1.6 to 12.3 ± 2.4 μmol/min · kg (P = 0.038). In the obese group, AT glucose uptake was impaired (5.0 ± 1.0 μmol/min · kg, P = 0.05 vs. the lean group), and bradykinin did not exert any metabolic action (6.0 ± 0.8 μmol/min · kg, P = 0.01 vs. the lean group).
  
  
  CONCLUSIONS
  AT blood flow is not an independent regulator of AT glucose metabolism. Insulin is a potent stimulator of AT blood flow, and bradykinin potentiates the hemodynamic and metabolic actions of insulin in lean but not in obese individuals.
authors.affiliation: Turku PET Centre, Turku University and Turku University Hospital, PL 52, 20521 Turku, Finland. patricia.iozzo@ifc.cnr.it
authors.forename: P
authors.initials: P
authors.lastname: Iozzo
authors.forename: A
authors.initials: A
authors.lastname: Viljanen
authors.forename: M A
authors.initials: MA
authors.lastname: Guzzardi
authors.forename: H
authors.initials: H
authors.lastname: Laine
authors.forename: M J
authors.initials: MJ
authors.lastname: Honka
authors.forename: E
authors.initials: E
authors.lastname: Ferrannini
authors.forename: P
authors.initials: P
authors.lastname: Nuutila
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007866:Leg / Q000098:blood supply / Q000503:physiopathology; D035002:Lower Extremity / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D009765:Obesity / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D012039:Regional Blood Flow / Q000502:physiology*; D013848:Thigh / Q000098:blood supply / Q000503:physiopathology; D013851:Thinness / Q000097:blood / Q000378:metabolism / Q000503:physiopathology
chemical_list: D007328:Insulin; D005947:Glucose; D001920:Bradykinin