Effects of prolonged pulsatile hyperinsulinemia in humans. Enhancement of insulin sensitivity.

Prolonged near-physiological pulsatile insulin infusion has a greater hypoglycemic effect than continuous insulin infusion. We have previously shown that continuous hyperinsulinemia induces insulin insensitivity. This study examines the mechanisms responsible for the greater hypoglycemic effect of pulsatile insulin administration, in particular, whether prolonged pulsatile hyperinsulinemia induces insulin insensitivity. Basally and 1 h after cessation of a 20-h pulsatile infusion of insulin (0.5 mU.kg-1.min-1), eight nondiabetic human subjects were assessed for 1) glucose turnover with [3-3H]glucose, 2) insulin sensitivity by minimal-model analysis of intravenous glucose tolerance tests, and 3) monocyte insulin-receptor binding. The time-averaged plasma insulin levels were 30 +/- 5 mU/L (mean +/- SE) during the infusion, which was similar to the levels achieved in our previous continuous hyperinsulinemia study. However, the average rate of glucose infusion to maintain euglycemia was 55% greater than in the previous study. Hepatic glucose production was -5.2 +/- 1.4 mumol.kg-1.min-1 during the infusion but returned to preinfusion levels 1 h after the infusion was stopped. Insulin sensitivity (Sl) and glucose tolerance (rate of glucose disappearance, Kg) showed changes opposite in direction to our previous continuous hyperinsulinemia study (pre- vs. postinfusion Kg 1.5 +/- 0.1 vs. 1.7 +/- 0.2 min-1 x 10(2), NS; pre- vs. postinfusion Sl 8.4 +/- 2.3 vs. 11.8 +/- 3.7 min-1.mU-1.L x 10(4), P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)