Limitations to exercise- and maximal insulin-stimulated muscle glucose uptake

The hypothesisof this investigation was that insulin and muscle contraction, byincreasing the rate of skeletal muscle glucose transport, would biascontrol so that glucose delivery to the sarcolemma (and t tubule) andphosphorylation of glucose intracellularly would exert more influenceover glucose uptake. Because of the substantial increases in blood flow(and hence glucose delivery) that accompany exercise, we predicted thatglucose phosphorylation would become more rate determining duringexercise. The transsarcolemmal glucose gradient (TSGG; the glucoseconcentration difference across the membrane) is inversely related tothe degree to which glucose transport determines the rate of glucoseuptake. The TSGG was determined by using isotopic methods in consciousrats during euglycemic hyperinsulinemia Ins; 20 mU/(kg · min); n = 7], during treadmill exercise (Ex,n = 6), and in sedentary,saline-infused rats (Bas, n = 13).Rats received primed, constant intravenous infusions of trace3-O-³H]methyl-D-glucoseand U-¹⁴C]mannitol.Then2-deoxy-³H]glucosewas infused for the calculation of a glucose metabolic index(R_g). At the end of experiments,rats were anesthetized, and soleus muscles were excised. Total soleusglucose concentration and the steady-state ratio of intracellular toextracellular3-O-³H]methyl-D-glucose(which distributes on the basis of the TSGG) were used to calculateranges of possible glucose concentrations (G]) at theinner and outer sarcolemmal surfaces(G]_im andG]_om, respectively).Soleus R_g was increased in Ins andfurther increased in Ex. In Ins, total soleus glucose,G]_om, and the TSGGwere decreased compared with Bas, whileG]_im remained near 0. In Ex, total soleus glucose andG]_im were increasedcompared with Bas, and there was not a decrease inG]_om as was observedin Ins. In addition, accumulation of intracellular free2-deoxy-³H]glucoseoccurred in soleus in both Ex and Ins. Taken together, these dataindicate that, in Ex, glucose phosphorylation becomes an importantlimitation to soleus glucose uptake. In Ins, both glucose delivery andglucose phosphorylation influence the rate of soleus glucose uptakemore than under basal conditions.