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. Pieber12 and
- Martin Ellmerer1
- 1Division of Diabetes and Metabolism, Department of Internal Medicine, Medical University Graz, Graz, Austria
- 2Joanneum Research Graz Forschungsgesellschaft mbH, Graz, Austria
- Address correspondence and reprint requests to Martin Ellmerer, PhD, Department of Internal Medicine: Diabetes and Metabolism, Center for Medical Research, Medical University Graz, Stiftingtalstrasse 24, 8010 Graz, Austria. E-mail: martin.ellmerer{at}healthgate.at
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.
RESEARCH DESIGN AND METHODS—In a randomized, controlled trial, euglycemic-hyperinsulinemic clamp (1.2 mU · kg−1 · min−1 insulin) and saline control experiments were performed in 10 healthy volunteers (aged 27.5 ± 4 years, 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 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.
Footnotes
-
Published ahead of print at http://diabetes.diabetesjournals.org on 29 June 2007. DOI: 10.2337/db07-0238.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0238.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
- Accepted June 15, 2007.
- Received March 14, 2007.
- DIABETES
