Disassociation of the plasma insulin response from the blood glucose concentration during glucose infusions in normal dogs

Abstract

Twenty-two anesthetized dogs were given a constant glucose infusion (14 mg/kg/min) for 360 min, while blood glucose concentration was continuously monitored. Plasma insulin concentration was measured every 30 min. The blood glucose peaked at 60 min and then steadily fell (mean fall, 56 mg 100 ml ), while plasma insulin continuously rose (mean rise, 65 μU/ml). This suggests that blood glucose concentratiion was not the primary stimulus for insulin secretion. In a second series of experiments, five dogs received glucose infusions as described above. One week later, each dog was reinfused with a larger total glucose load, regulated by continuous blood glucose monitoring to exactly reproduce the blood glucose response observed during the first infusion. Plasma insulin concentrations during the high load infusions were significantly higher than during the low load infusions. Thus, changes in glucose load produced changes in plasma insulin concentration, even though blood glucose levels were held constant. Thus, using two different approaches, we have demonstrated that plasma insulin levels can be dissociated from the coexisting blood glucose concentration. These results suggest that the level of blood glucose may not be the primary determinant of the insulin response to glucose during the chronic phase of insulin secretion.