Differential effects of insulin and hyperglycemia on intracellular glucose disposition in humans

Insulin stimulates both glucose oxidation and nonoxidative glucose disposal (glycogen and lipid synthesis, anaerobic glycolysis) in vivo. The influence of hyperglycemia per se on these two major pathways of intracellular glucose disposition has not been established. Whole-body glucose oxidation (by continuous indirect calorimetry) and total glucose turnover (by the glucose clamp technique) were measured in six healthy volunteers under four different experimental conditions: (protocol A) insulin was infused at a rate of 1 mU/min/kg while euglycemia (92 +/- 1 mg/100 mL) was maintained by an exogenous glucose infusion (8.05 +/- 0.94 mg/min/kg over three hours); (protocol B) the insulin infusion was halved but the same glucose infusion was given, thereby raising plasma glucose levels to a plateau of 144 +/- 14 mg/100 mL over the third hour; (protocol C) the insulin infusion was further reduced to 0.25 mU/min/kg, but the glucose infusion rate was left unchanged, whereby plasma glucose plateaued at 275 +/- 21 mg/100 mL; and (protocol D) the insulin infusion rate was 0.5 mU/min/kg), but the glucose infusion was adjusted (5.03 +/- 0.69 mg/min/kg) to maintain euglycemia. In all protocols, somatostatin was used to block endogenous insulin response. Under euglycemic conditions (protocols A and D), the presence of higher plasma insulin levels (80 +/- 6 v 39 +/- 5 microU/mL) caused the expected stimulation of both glucose oxidation (4.08 +/- 0.29 v 3.27 +/- 0.36 mg/min/kg) and nonoxidative glucose uptake (4.84 +/- 0.67 v 2.96 +/- 0.77 mg min/kg).(ABSTRACT TRUNCATED AT 250 WORDS)