Interaction between insulin sensitivity and muscle perfusion on glucose uptake in human skeletal muscle - Evidence for capillary recruitment

Insulin and glucose delivery (muscle perfusion) can modulate insulin-mediat ed glucose uptake. This study was undertaken to determine 1) to a-hat exten t insulin sensitivity modulates the effect of perfusion on glucose uptake a nd 2) whether this effect is achieved via capillary recruitment. Tee measur ed glucose disposal rates (GDRs) and leg muscle glucose uptake (LGU) in sub jects exhibiting a wide range of insulin sensitivity; after 4 h of steady-s tate (SS) euglycemic hyperinsulinemia (>6,000 pmol/l) and subsequently afte r raising the rate of leg blood flow (LBF) 2-fold with a superimposed intra femoral artery infusion of methacholine chloride (Mch), an endothelium-depe ndent vasodilator. LBF was determined by thermodilution: LGU = arteriovenou s glucose difference (AVG Delta) x LBF. As a result of the 114 +/- 12% incr ease in LBF induced by Mch, the AVG Delta decreased 32 +/- 4%, and overall rates of LGU increased 40 +/- 5% (P < 0.05). We found a positive relationsh ip between the Mch-modulated increase in LGU and insulin sensitivity (GDR) (r = 0.60, P < 0.02), suggesting that the most insulin-sensitive subjects h ad the greatest enhancement of LGU in response to augmentation of muscle pe rfusion. In separate groups of subjects, we also examined the relationship between muscle perfusion rate and glucose extraction (AVG Delta). Perfusion was either pharmacologically enhanced with Mch or reduced intra-arterial i nfusion of the nitric oxide inhibitor N-G-monomethyl-L-arginine during SS e uglycemic hyperinsulinemia. Over the range of LBF, changes in AVG Delta wer e smaller than expected based on the noncapillary recruitment model of Renk in. Together, the data indicate that 1) muscle perfusion becomes more rate Limiting to glucose uptake as insulin sensitivity increases and 2) insulin- mediated increments in muscle perfusion are accompanied by capillary recrui tment. Thus, insulin-stimulated glucose uptake displays both permeability- and perfusion-limited glucose exchange properties.