A microdialysis method for the in situ investigation of the action of large peptide molecules in human skeletal muscle: detection of local metabolic effects of insulin

The possibility of using microdialysis catheters with a large pore size dia lysis membrane (100 kDa) to investigate the action of macromolecules perfus ed into the interstitial space of peripheral tissues was explored. This was made possible by increasing the colloid osmotic pressure of the perfusate with 40 g/l of dextran-70 to prevent perfusate loss across the dialysis mem branes. Microdialysis catheters were inserted into the quadriceps femoris m uscle of 13 human subjects. With different perfusion flow rates (1.33, 0.66 , 0.33 and 0.16 mu l/min) the recorded concentrations of glucose, lactate, and urea were in agreement with values previously obtained using a conventi onal membrane with a smaller pore size (20 kDa) [Rosdahl H, Hamrin K, Unger stedt U, Henriksson. J Am J Physiol 1998;274:E936-45.]. When insulin was ad ded to the perfusate, the concentration of glucose was significantly reduce d, indicating that insulin diffuses across the dialysis membrane and has ce llular effects that can be simultaneously recorded. The present findings ar e the first documentation on the use of microdialysis to study the local me tabolic action of large peptide molecules in human tissues and may open new avenues for in-vivo metabolic research. (C) 2000 Elsevier Science B.V. All rights reserved.