Transcapillary insulin transfer in human skeletal muscle.
BACKGROUND
Transcapillary insulin transfer is considered a rate-limiting step in insulin action at supraphysiological insulin concentrations. However, it remains unclear whether this concept also applies for physiological conditions.


METHODS
In the present study we set out to characterize transcapillary insulin transfer by measuring insulin concentrations in plasma and interstitial space fluid of skeletal muscle during an oral glucose tolerance test and euglycaemic hyperinsulinaemic clamp conditions, respectively. For this purpose we employed in vivo microdialysis of skeletal muscle in conjunction with an ultrasensitive insulin assay in eight healthy lean male volunteers (aged 25 +/- 1 years).


RESULTS
Insulin concentrations at baseline were 48 +/- 8 pmol x L(-1) in plasma and 19 +/- 4 pmol x L(-1) in the interstitium (P = 0.002). The mean interstitium to plasma ratio at baseline was 0.48 +/- 0.09 pmol x L(-1). During the oral glucose tolerance test the interstitium to plasma ratio remained unchanged (0.43 +/- 0.12, P = NS vs. baseline), but was significantly reduced during euglycaemic hyperinsulinaemic clamp conditions at steady-state hyperinsulinaemia (0.12 +/- 0.01, P = 0.01 vs. baseline).


CONCLUSIONS
In summary there is a substantial transcapillary insulin gradient in healthy human skeletal muscle under baseline and glucose-stimulated conditions. Our findings support the hypothesis of a saturable transcapillary insulin transport representing a partly rate-limiting step for insulin action.
Herkner
H
H
Department of Clinical Pharmacology, University of Vienna, Medical School, Vienna, Austria.
Klein
N
N
Joukhadar
C
C
Lackner
E
E
Langenberger
H
H
Frossard
M
M
Bieglmayer
C
C
Wagner
O
O
Roden
M
M
Müller
M
M
D000328:Adult; D002196:Capillaries / Q000378:metabolism; D002199:Capillary Permeability; D018592:Cross-Over Studies; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000098:blood supply*
D007328:Insulin