Functional limitations to glucose uptake in muscles comprised of differentfiber types

Skeletal muscle glucose uptake requires delivery of glucose to the sarcolem ma, transport across the sarcolemma, and the irreversible phosphorylation o f glucose by hexokinase (HK) inside the cell. Here, a novel method was used in the conscious rat to address the roles of these three steps in controll ing the rate of glucose uptake in soleus, a muscle comprised of type I fibe rs, and two muscles comprised of type II fibers. Experiments were performed on conscious rats under basal conditions or during hyperinsulinemic euglyc emic clamps. Rats received primed, constant infusions of 3-O-methyl-[H-3]gl ucose (3-O-MG) and [1-C-14]mannitol. Total muscle glucose concentration and the steady-state ratio of intracellular to extracellular 3-O-MG concentrat ion, which distributes based on the transsarcolemmal glucose gradient (TSGG ), were used to calculate glucose concentrations at the inner and outer sar colemmal surfaces ([G](im) and [G](om), respectively) in muscle. Muscle glu cose uptake was much lower in muscle comprised of type II fibers than in so leus under both basal and insulin-stimulated conditions. Under all conditio ns, the TSGG in type II muscle exceeded that in soleus, indicating that glu cose transport plays a more important role to limit glucose uptake in type II muscle. Although hyperinsulinemia increased [G](im) in soleus, indicatin g that phosphorylation was a limiting factor, type II muscle was limited pr imarily by glucose delivery and glucose transport. In conclusion, the relat ive importance of glucose delivery, transport, and phosphorylation in contr olling the rate of insulin-stimulated muscle glucose uptake varies between muscle fiber types, with glucose delivery and transport being the primary l imiting factors in type II muscle.