Effects of short-term pulsatile and continuous insulin delivery on glucagon secretion and insulin secretion and action

Abstract

In six normal nonobese subjects, hyperinsulinemic euglycemic clamps were performed during paired sequential two-hour intravenous (IV) insulin infusions separated by an hour washout period. Each infusion was either 32 mU/kg/h of continuous insulin (CI) or 75% of this dose as 40-second pulses delivered every 13 minutes (PI). Six studies were performed with each of the following sequences in random order: PI-CI, CI-PI, and CI-CI. Based on the initial infusions, the insulin-dependent fractional glucose disappearance rate (X) during pulsatile insulin delivery (3.0 ± 0.4 min −1 × 10 2, n = 6) was 73% of that of the continuous infusions (4.1 ± 0.3 min −1 × 10 2, n = 12). This ratio was similar to that of the measured time-averaged plasma insulin areas (PI = 24.7 ± 3.8 v CI = 31.4 ± 3.5 mU/L). There was an average 23% enhancement of insulin's hypoglycemic effect during the second 12 CI infusions compared with the 12 initial CI infusions (X = 5.1 ± 0.5 v 4.1 ± 0.3 min −1 × 10 2, P < .05). There was no significant difference between the enhancing effects of PI and CI infusions on insulin action in the subsequent CI's (X = 4.9 ± 0.9 for PI-CI v X = 5.3 ± 0.2 min −1 × 10 2 for CI-CI). First infusion PI significantly ( P < .05) decreased plasma C-peptide levels (0.34 ± 0.05 to 0.20 ± 0.06 μmol/L), whereas CI did not (0.33 ± 0.02 to 0.32 ± 0.07). Plasma glucagon remained suppressed (14 ± 4 ng/L) one hour after the first infusion of PI, but returned to baseline one hour after the first infusion of CI (29 ± 4). In conclusion, although PI administration over two hours did not produce greater hypoglycemic effect or greater enhancement of subsequent insulin action, pulsatile hyperinsulinemia over two hours in normal subjects produces greater suppression of insulin secretion and longer-lasting suppression of glucagon secretion than CI infusion. The latter may be of importance of the evolution of the greater hypoglycaemic potency of longer-term PI delivery.