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 dialysis membrane (100 kDa) to investigate the action of macromolecules perfused 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 membranes. Microdialysis catheters were inserted into the quadriceps femoris muscle of 13 human subjects. With different perfusion flow rates (1. 33, 0.66, 0.33 and 0.16 microl/min) the recorded concentrations of glucose, lactate, and urea were in agreement with values previously obtained using a conventional membrane with a smaller pore size (20 kDa) [Rosdahl H, Hamrin K, Ungerstedt U, Henriksson. J Am J Physiol 1998;274:E936-45.]. When insulin was added to the perfusate, the concentration of glucose was significantly reduced, indicating that insulin diffuses across the dialysis membrane and has cellular effects that can be simultaneously recorded. The present findings are the first documentation on the use of microdialysis to study the local metabolic action of large peptide molecules in human tissues and may open new avenues for in-vivo metabolic research.
Rosdahl
H
H
Department of Physiology and Pharmacology, Karolinska Institutet, S-17177, Stockholm, Sweden.
Hamrin
K
K
Ungerstedt
U
U
Henriksson
J
J
D000328:Adult; D003911:Dextrans; D004058:Diffusion; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008567:Membranes, Artificial; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D014508:Urea / Q000378:metabolism
D003911:Dextrans; D007328:Insulin; D008567:Membranes, Artificial; D010455:Peptides; D019344:Lactic Acid; D014508:Urea; D005947:Glucose