SKELETAL-MUSCLE BLOOD-FLOW INDEPENDENTLY MODULATES INSULIN-MEDIATED GLUCOSE-UPTAKE

Insulin-mediated glucose uptake (IMGU) occurs principally in skeletal muscle. To directly examine whether skeletal muscle perfusion (F) can directly and independently modulate IMGU, we combined the hyperinsulin emic euglycemic clamp and leg balance techniques [leg glucose uptake ( LGU) = arteriovenous glucose difference (Delta AVG) x F]. Young (< 40 yr) healthy lean subjects were studied during euglycemic hyperinsuline mia of similar to 23 mu U/ml (group I, n = 8) and similar to 950 mu U/ ml (group II, n = 6). Femoral Delta AVG and leg F were measured, and L GU was calculated at baseline after similar to 200 min of steady-state hyperinsulinemia alone and during a superimposed intrafemoral artery infusion of methacholine hydrochloride designed to increase leg F two- to threefold. In groups I and II, insulin raised the Delta AVG simila r to 4- and 14-fold, respectively (P < 0.0001). Leg F was unchanged du ring the low-dose insulin infusion (group I) but increased 112 +/- 35% in group II (P < 0.001). During methacholine infusion the Delta AVG n arrowed 35.9 +/- 6.8% (P < 0.01) and 20.5 +/- 4.8% (P < 0.05) in group s I and II, respectively. Leg F rose 224 +/- 30% (P < 0.01) and 79 +/- 13% (P < 0.05) above the flow rate achieved with insulin alone. Thus, during methacholine flow modulation, LGU increased 116 +/- 36% (P < 0 .01) and 47 +/- 11% (P < 0.05) in groups I and II, respectively. In co nclusion, skeletal muscle perfusion during hyperinsulinemia can act as an independent determinant of IMGU.