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

Abstract

A B S T R A C T Plasma insulin concentrations afterpulse 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 1251-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 glucoseinduced posthepatic insulin delivery rate minute by minute.Under basal conditions, 2.64+0.28 (mean±SEM) mU/min m2 reaches the systemic circulation. In the 90 min that follow acute glucose stimulation, 0.86+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 m2.The delivery curves were closely (mean squared deviation of4.5+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.Received for publication 11 April 1978 and in revised form 5 March 1979. Both the first and the second spike ofinsulin 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.

Scintigraphic distribution of 123 I labelled proinsulin, split conversion intermediates and insulin in rats

“…In vivo, monoiodinated insulin seems to be cleared as fast as native insulin although this is not fully agreed upon [27][28][29][30].…”

Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR).

“…Fasting posthepatic insulin delivery rate (IDR) was then obtained as the product of posthepatic insulin clearance by fasting plasma insulin concentration (25).…”

Beta cell function and its relation to insulin action in humans: a critical appraisal

“…Thus, insulin resistant subjects usually show a decrease in insulin clearance [18]. The application of decovolution analysis (initially used with insulin [19]) to plasma C-peptide concentrations [20] and the validation of a standard plasma C-peptide disappearance function [21] have made it possible to reconstruct insulin secretory rates from peripheral C-peptide concentrations independently of insulin clearance. Clearly, while plasma insulin concentrations are the most important determinant of insulinmediated glucose disposal, to assess beta cell function true insulin secretion rates should be measured whenever possible.…”

“…When given as a bolus (as in the IVGTT), intravenous glucose triggers a variable multiphasic secretory response, in which one or two secondary peaks, in phase with corresponding plasma glucose peaks, can often be discerned [19]. For this reason, only the first burst of insulin release is usually considered.…”