title: Physiological hyperinsulinemia has no detectable effect on access of macromolecules to insulin-sensitive tissues in healthy humans.
abstract: OBJECTIVE
  Physiologically elevated insulin concentrations promote access of macromolecules to skeletal muscle in dogs. We investigated whether insulin has a stimulating effect on the access of macromolecules to insulin-sensitive tissues in humans as well.
  
  
  METHODS
  In a randomized, controlled trial, euglycemic-hyperinsulinemic clamp (1.2 mU x kg(-1) x min(-1) insulin) and saline control experiments were performed in 10 healthy volunteers (aged 27.5 +/- 4 years, BMI 22.6 +/- 1.6 kg/m(2)). Distribution and clearance parameters of inulin were determined in a whole-body approach, combining primed intravenous infusion of inulin with compartment modeling. Inulin kinetics were measured in serum using open-flow microperfusion in interstitial fluid of femoral skeletal muscle and subcutaneous adipose tissue.
  
  
  RESULTS
  Inulin kinetics in serum were best described using a three-compartment model incorporating a serum and a fast and a slow equilibrating compartment. Inulin kinetics in interstitial fluid of peripheral insulin-sensitive tissues were best represented by the slow equilibrating compartment. Serum and interstitial fluid inulin kinetics were comparable between the insulin and saline groups. Qualitative analysis of inulin kinetics was confirmed by model-derived distribution and clearance parameters of inulin. Physiological hyperinsulinemia (473 +/- 6 vs. 18 +/- 2 pmol/l for the insulin and saline group, respectively; P < 0.001) indicated no effect on distribution volume (98.2 +/- 6.2 vs. 102.5 +/- 5.7 ml/kg; NS) or exchange parameter (217.6 +/- 34.2 vs. 243.1 +/- 28.6 ml/min; NS) of inulin to peripheral insulin-sensitive tissues. All other parameters identified by the model were also comparable between the groups.
  
  
  CONCLUSIONS
  Our data suggest that in contrast to studies performed in dogs, insulin at physiological concentrations does not augment recruitment of insulin-sensitive tissues in healthy humans.
authors.affiliation: Division of Diabetes and Metabolism, Department of Internal Medicine, Medical University Graz, Graz, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Weinhandl
authors.forename: Christoph
authors.initials: C
authors.lastname: Pachler
authors.forename: Julia K
authors.initials: JK
authors.lastname: Mader
authors.forename: Dimas
authors.initials: D
authors.lastname: Ikeoka
authors.forename: Agnes
authors.initials: A
authors.lastname: Mautner
authors.forename: Andreas
authors.initials: A
authors.lastname: Falk
authors.forename: Maria
authors.initials: M
authors.lastname: Suppan
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.forename: Martin
authors.initials: M
authors.lastname: Ellmerer
mesh_terms: D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure; D004285:Dogs; D005919:Glomerular Filtration Rate; D015309:Glucose Clamp Technique; D006339:Heart Rate; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D023421:Models, Animal; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D007328:Insulin