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This Article Full Text Full Text (PDF) All Versions of this Article: 289/2/E296    most recent 00431.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Bodenlenz, M. Articles by Pieber, T. R. Search for Related Content PubMed PubMed Citation Articles by Bodenlenz, M. Articles by Pieber, T. R.

Measurement of interstitial insulin in human adipose and muscle tissue under moderate hyperinsulinemia by means of direct interstitial access

¹Department of Internal Medicine, Diabetes, and Metabolism, Medical University Graz, ²Institute of Medical Technologies and Health Management, Joanneum Research, and ³Department of Biophysics, Institute of Biomedical Engineering, Graz University of Technology, Graz, Austria

Submitted 10 September 2004 ; accepted in final form 7 March 2005

Insulin’s action to stimulate glucose utilization is determined by the insulin concentration in interstitial fluid (ISF) of insulin-sensitive tissues. The concentration of interstitial insulin has been measured in human subcutaneous adipose tissue and skeletal muscle, however, never in parallel. The aim of this study was to compare interstitial insulin levels between both tissue beds by simultaneous measurements and to verify and quantify low peripheral ISF insulin fractions as found during moderate hyperinsulinemia. Nine healthy subjects (27.2 ± 0.8 yr) were investigated. A euglycemic-hyperinsulinemic clamp was started with a primed-constant intravenous insulin infusion of 1 mU·kg^–1·min^–1. For direct access to ISF, macroscopically perforated open-flow microperfusion catheters were inserted in both tissues. During steady-state conditions (9.5 h), interstitial effluents were collected in 30-min fractions using five different insulin concentrations in the inflowing perfusates ("no net flux" protocol). Regression analysis of insulin concentrations in perfusates and effluents yielded the relative recovery and the perfusate insulin concentration, which was in equilibrium with the surrounding tissue. Thus, in subcutaneous adipose tissue and skeletal muscle, the mean ISF-to-serum insulin level was calculated as 21.0% [95% confidence interval (CI) 17.5–24.5] and 26.0% (95% CI 19.1–32.8; P = 0.14), respectively. Recoveries for insulin averaged 51 and 64%, respectively. The data suggest that the concentrations of insulin arising in healthy subjects at the level of ISF per se are comparable between subcutaneous adipose and skeletal muscle tissue. The low interstitial insulin fractions seem to confirm reports of low peripheral insulin levels during moderate insulin clamps.

extracellular fluid; euglycemic-hyperinsulinemic glucose clamp; open-flow microperfusion; no net flux; equilibrium method

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