title: Insulin-mediated increases in renal plasma flow are impaired in insulin-resistant normal subjects.
abstract: BACKGROUND
  Impaired vasodilatation in skeletal muscle is a possible mechanism linking insulin resistance to blood pressure regulation. Increased renal vascular resistance has been demonstrated in the offspring of essential hypertensives. We assessed whether insulin-mediated renal vasodilatation is impaired in insulin-resistant normal subjects.
  
  
  METHODS
  In two groups of 10 insulin-resistant and 10 insulin-sensitive normal subjects, we compared the effects of sequential physiological and supraphysiological insulin dosages (50 and 150 mU kg(-1) h(-1)) on renal plasma flow (RPF) and leg blood flow using the euglycaemic clamp technique, 131I-labelled Hippuran clearances and venous occlusion plethysmography. Time-control experiments were performed in the same subjects.
  
  
  RESULTS
  Whole-body glucose uptake amounted to 4.9 +/- 2.1 and 11.0 +/- 2.4 mg kg(-1) min(-1) in the insulin-resistant and to 12.7 +/- 2.3 and 17.4 +/- 2.6 mg kg(-1) min(-1) in the insulin-sensitive subjects during physiological and supraphysiological hyperinsulinaemia, respectively. RPF increased more in insulin-sensitive compared to insulin-resistant subjects during physiological hyperinsulinaemia (13.7 vs. 6.8%, P < 0.05). RPF increased to comparable levels during supraphysiological hyperinsulinaemia. Insulin-mediated changes in leg blood flow did not differ between groups. In the combined group, we found a positive correlation between insulin-mediated glucose uptake and changes in RPF during physiological hyperinsulinaemia (r = 0.57, P = 0.009), whereas insulin-mediated glucose uptake correlated with changes in leg blood flow during supraphysiological hyperinsulinaemia (r = 0.54. P = 0.017).
  
  
  CONCLUSIONS
  Our results suggest that the sensitivities of the skeletal muscle and renal vascular bed differ for insulin's vasodilatory action. Insulin-mediated increases in RPF are impaired in insulin-resistant but otherwise normal subjects during physiological hyperinsulinaemia.
authors: University Hospital Groningen, Groningen, The Netherlands. j.c.ter.maaten@int.azg.nl
authors: J C
authors: JC
authors: Ter Maaten
authors: S J
authors: SJ
authors: Bakker
authors: E H
authors: EH
authors: Serné
authors: H J
authors: HJ
authors: Moshage
authors: A J
authors: AJ
authors: Donker
authors: R O
authors: RO
authors: Gans
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D007866:Leg / Q000098:blood supply; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D017595:Renal Plasma Flow / Q000187:drug effects; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin