Glucose effectiveness is the major determinant of intravenous glucose tolerance in the rat

To determine the importance of insulin for glucose disposal during an intravenous glucose tolerance test in rats, experiments were performed in four cohorts of conscious unrestrained rats fasted overnight. In cohorts 1-3, a bolus of tracer ([3-3H]glucose, 50 microCi) was given alone, with glucose (0.3 g/kg) to induce an endogenous insulin response (approximately 1,100 pmol/l), or with exogenous insulin to give physiological (1,700 pmol/l) or supraphysiological (12,000 pmol/l) plasma levels. Raising plasma insulin within the physiological range had no effect (P > 0.05), but supraphysiological levels induced hypoglycemia (7.3 +/- 0.2 to 3.6 +/- 0.2 mmol/l) and increased [3H]glucose disappearance rate (P < 0.001). In cohort 4, a primed, continuous tracer infusion was started 120 min before saline or glucose bolus injection. [3H]glucose levels fell 15-20%, and the disappearance rate rose 36% (P < 0.05) after glucose injection. These results indicate that in fasted rats a tracer bolus injection protocol is not sufficiently sensitive to measure the physiological effect of insulin released in response to a bolus of glucose because this effect of insulin is small. Glucose itself is the predominant mediator of glucose disposal after a bolus of glucose in the fasted rat.