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Diabetes Publish Ahead of Print published online ahead of print June 29, 2007
DOI: 10.2337/db07-0238
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Original Research

Physiological Hyperinsulinemia has No Detectable Effect on Access of Macromolecules to Insulin-sensitive Tissues in Healthy Humans

Heinz Weinhandl1, Christoph Pachler1, Julia K. Mader1, Dimas Ikeoka1, Agnes Mautner2, Andreas Falk2, Maria Suppan2, Thomas R. Pieber1,,2, and Martin Ellmerer1

1Department of Internal Medicine, Diabetes and Metabolism, Medical University Graz, Auenbruggerplatz 15, A-8036 Graz, Austria
2Joanneum Research Graz Forschungsgesellschaft mbH, Elisabethstrasse 11a, A-8010 Graz, Austria

Correspondence: martin.ellmerer{at}healthgate.at

Key Words: inulin • three-compartment model • tissue recruitment • open-flow microperfusion

Objective.: Physiologically elevated insulin concentrations promote access of macromolecules to skeletal muscle in dogs. We investigated, whether also in humans, insulin has a stimulating effect on the access of macromolecules to insulin-sensitive tissues.

Research Design and Methods.: In a randomized controlled trial euglycemic hyperinsulinemic clamp (insulin: 1.2 mU·kg-1·min-1) vs. saline control experiments were performed in 10 healthy volunteers (27.5±4 yrs, BMI: 22.6±1.6 kg/m2). Distribution and clearance parameters of inulin were determined in a whole body approach, combining primed intravenous infusion of inulin with compartment modeling. Inulin kinetics was measured in serum and using open-flow microperfusion in interstitial fluid of femoral skeletal muscle and subcutaneous adipose tissue.

Results.: Inulin kinetics in serum was best described using a three-compartment model incorporating a serum, a fast and a slow equilibrating compartment. Inulin kinetics in interstitial fluid of peripheral insulin-sensitive tissues was best represented by the slow equilibrating compartment. Serum and interstitial fluid inulin kinetics was comparable between insulin and saline group. Qualitative analysis of inulin kinetics was confirmed by model derived distribution and clearance parameters of inulin. Physiological hyperinsulinemia (insulin: 473±6pM vs. saline: 18±2; P < 0.001) indicated no effect on distribution volume (insulin: 98.2±6.2ml/kg vs. saline: 102.5±5.7; NS) or exchange parameter (insulin: 217.6±34.2 vs. saline: 243.1±28.6 ml/min; NS) of inulin to peripheral insulin-sensitive tissues. Also all other parameters identified by the model were comparable between 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.


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