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

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 X 10(2), n = 6) was 73% of that of the continuous infusions (4.1 +/- 0.3 min-1 X 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 X 10(2), P less than .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 X 10(2) for CI-CI). First infusion PI significantly (P less than .05) decreased plasma C-peptide levels (0.34 +/- 0.05 to 0.20 +/- 0.06 mumol/L), whereas CI did not (0.33 +/- 0.02 to 0.32 +/- 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)