Pattern of insulin delivery after intravenous glucose injection in man and its relation to plasma glucose disappearance

Abstract

Plasma insulin concentrations after pulse intravenous injection of glucose show an early rise, which declines towards the prestimulation level smoothly. This pattern is the effect of both continuing secretion and hormone disappearance from the plasma. To reconstruct the time-course of the actual secretory response, we measured insulin disappearance from the plasma of 17 healthy volunteers by means of a bolus intravenous injection of 125I-insulin, and then performed an intravenous glucose tolerance test with frequent blood sampling. The data were analyzed by deconvolution, which made it possible to compute the glucose-induced posthepatic insulin delivery rate minute by minute. Under basal conditions, 2.64 ± 0.28 (mean ± SEM) mU/min x m2 reaches the systemic circulation. In the 90 min that follow acute glucose stimulation, 086 ± 0.11 U/m2, a 270% increment over the basal production rate, is made available to the periphery. A wide individual variability was found to exist in both the basal and the glucose-stimulated delivery. They were strongly (P < 0.001) related to each other in a direct fashion. A first spike of insulin release (107 ± 12 mU/min) occurred in all the subjects at 2.2 ± 0.2 min followed, in 16 subjects, by a second spike (38 ± 6 mU/min), at 11.3 ± 0.9 min. Two-thirds of the total postglucose insulin output were associated with the initial, oscillatory phase (from 0 to 25 min, on average), and one-third with the 'tail' phase (from 25 to 90 min), during which the average delivery rate was 5.0 ± 0.9 mU/min x m2. The delivery curves were closely (mean squared deviation of 4.5 ± 0.5 mU/min) reproduced by computer simulation upon assuming that insulin secretion is a function of both glucose concentration and glucose rate of change. Both the first and the second spike of insulin delivery, but not the total insulin output during the test, showed a significant, positive correlation with the plasma glucose disappearance rate computed between 10 and 60 min. Furthermore, with a time shift of ≃ 15 min, a significant relationship between the phases of insulin secretion and the glucose decay rates, computed over corresponding time intervals, was evident throughout the test.