Measurement by microdialysis of the insulin concentration in subcutaneous interstitial fluid. Importance of the endothelial barrier for insulin.

To evaluate the interstitial insulin and inulin concentrations, 20-min microdialysis samples from the abdominal subcutaneous tissue were obtained by using two 45-mm polypropylene dialyzing tubes (o.d. approximately 0.5 mm, pore size 0.2 micron) during a euglycemic hyperinsulinemic (120 mU.m-2 x min-1) clamp (n = 9) or during a constant inulin infusion (n = 5). After in situ calibration of the microdialysis catheters during steady-state conditions, interstitial and plasma insulin concentrations were estimated to 654 +/- 102 and 1176 +/- 66 pM, respectively, i.e., a 44% difference (P < 0.001). A doubling of the insulin infusion rate (240 mU.m-2 x m-1), leading to supraphysiological plasma insulin levels, raised the interstitial insulin concentrations markedly slower (approximately 20 min) than in plasma. Moreover, at steady state the concentration difference in the two compartments prevailed even during the high insulin infusion rate (55% difference, P < 0.01). In contrast, the interstitial inulin levels were similar to the plasma concentrations in subjects given a constant inulin infusion. Thus, the data suggest the presence of an endothelial barrier for insulin in the subcutaneous tissue. This barrier, in combination with tissue clearance of insulin, leads to lower insulin levels and altered kinetics with a slower rise in the interstitial fluid compared with plasma.