Extracellular glucose distribution is not altered by insulin: analysis of plasma and interstitial L-glucose kinetics

We examined the effects of insulin on leg blood flow, whole body extracellular glucose distribution, and glucose diffusion into the interstitial fluid (ISF) surrounding skeletal muscle cells in anesthetized dogs. Extracellular glucose distribution and glucose diffusion into the muscle ISF were assessed by studying the kinetics of L-[1-14C]glucose in plasma and hindlimb lymph. Femoral artery blood flow was not increased with insulin (7.9 +/- 0.7 vs. 7.1 +/- 1.4 ml.min-1.kg-1; P = 0.54). Plasma and lymph dynamics of L-glucose after intravenous administration were superimposable between saline and insulin infusion experiments, indicating that insulin did not affect L-glucose disappearance from plasma or appearance in muscle ISF. Plasma L-glucose kinetics were best described by a four-compartment model, and one of the remote pools (intermediate) predicted the lymph L-glucose dynamics well. Estimation of maximum glucose diffusion capacity indicated that this pool, rather than the slowest pool, represents insulin-sensitive tissues. In conclusion, our data indicate that insulin does not increase transcapillary glucose diffusion to insulin-sensitive cells. In addition, hindlimb lymph represents primarily skeletal muscle ISF, which is represented by an intermediate, rather than the slowest, remote pool from whole body compartmental analysis.