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 obt ained by using two 45-mm polypropylene dialyzing tubes (o.d. approxima tely 0.5 mm, pore size 0.2 mum) during a euglycemic hyperinsulinemic ( 120 mU . m-2 . min-1) clamp (n = 9) or during a constant inulin infusi on (n = 5). After in situ calibration of the microdialysis catheters d uring steady-state conditions, interstitial and plasma insulin concent rations were estimated to 654 +/- 102 and 1176 +/- 66 pM, respectively , i.e., a 44% difference (P < 0.001). A doubling of the insulin infusi on rate (240 mU . m-2 . min-1), leading to supraphysiological plasma i nsulin levels, raised the interstitial insulin concentrations markedly slower (approximately 20 min) than in plasma. Moreover, at steady sta te 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 co ncentrations in subjects given a constant inulin infusion. Thus, the d ata suggest the presence of an endothelial barrier for insulin in the subcutaneous tissue. This barrier, in combination with tissue clearanc e of insulin, leads to lower insulin levels and altered kinetics with a slower rise in the interstitial fluid compared with plasma.