Evidence that glucose transport is rate-limiting for in vivo glucose uptake

Abstract To determine whether glucose transport or intracellular glucose metabolism is rate-limiting for in vivo glucose uptake, rates of glucose disposal were measured in a group of normal subjects at varying levels of hyperglycemia designed to attain saturating rates of glucose disposal at low and high physiological insulin concentrations. At insulin levels of approximately 200 pmol/L, glucose disposal rates were 2.9 ± 0.4, 4.7 ± 0.5, 6.4 ± 0.6, and 6.5 ± 0.8 mg/kg/min at plasma glucose concentrations of 5.55, 11.10, 13.88, and 19.43 mmol/L (or 100, 200, 250, and 350 mg/dL, respectively). At insulin levels of approximately 750 pmol/L, glucose disposal rates were 1.7 to 2.1-fold higher: 6.2 ± 0.7, 9.2 ± 1.1, 11.0 ± 1.1, and 12.3 ± 1.4 mg/kg/min at glucose levels of 5.55, 11.10, 13.88, and 19.43 mmol/L. Thus, during both the 15- and 40-mU/m 2 /min insulin infusions, glucose disposal increased in a linear fashion from 5.55 to 13.88 mmol/L ( r = .90) and then effectively plateaued at the same plasma glucose level. If the plateau of glucose disposal during the 40-mU/m 2 /min insulin infusion was due to saturation of the intracellular capacity to metabolize glucose, then when plasma glucose was increased from 13.88 to 19.43 mmol/L at the lower insulin level, the glucose disposal should have continued to increase and not plateau, since the rate of glucose disposal was only approximately 50% of that attained at the higher insulin infusion rate. These results indicate that glucose uptake is a saturable system, and the similar plasma glucose at which glucose disposal plateaus during low- and higher-dose insulin infusions is consistent with the idea that glucose transport is rate-limiting for overall glucose disposal, and that insulin increases the maximal capacity of the glucose uptake system.