We studied the dose-response characteristics of insulin’s ability to modulate its own secretion in normal and type II diabetic (NIDDM) subjects by measuring suppression of serum C-peptide levels during insulin infusions witK the plasma glucose level held constant. In normal subjects at euglycemia, primed continuous insulin infusion rates of 15, 40, 120, and 240 mU/M2 min acutely raised serum insulin to steady state levels of 37 ± 2 (±SE), 96 ± 6, 286 ± 17, and 871 ± 93 µU/ml, respectively. During each infusion, maximal suppression of C-peptide to 30% of basal levels occurred by 130 min. At the higher insulin levels (≤100 µU/ml), C-peptide levels fell rapidly, with an apparent t½, of 13 min, which approximates estimates for the t½ of circulating C-peptide in man. This is consistent with an immediate 70% inhibition of the basal rate of insulin secretion. At the lower insulin level (37 ± 2 µU/ml), C-peptide levels fell to 30% of basal values less rapidly (apparent t½, 33 min), suggesting that 70% inhibition of basal insulin secretion rates was achieved more slowly. In NIDDM subjects, primed continuous insulin infusion rates of 15, 40, 120, and 1200 mU/M2-min acutely raised serum insulin to steady state levels of 49 ± 7, 93 ± 11, 364 ± 31, and 10, 003 ± 988 µU/ml. During studies at basal hyperglycemia, only minimal C-peptide suppression was found, even at pharmacological insulin levels (10, 003 ± 988 µU/ml). However, if plasma glucose was allowed to fall during the insulin infusions, there was a rapid decrease in serum C-peptide to 30% of basal levels, analogous to that in normal subjects. Three weeks of intensive insulin therapy did not alter C-peptide suppression under conditions of hyperinsulinemia and falling plasma glucose. The following conclusions were reached. 1) In normal subjects, insulin (40-1000 µU/ml) inhibits its own secretion in a dose-responsive manner; more time is required to achieve maximal 70% suppression at the lower insulin level (40 µU/ml). 2) In NIDDM studied at basal hyperglycemia, insulin has minimal ability to suppress its own secretion. Thus, impaired feedback inhibition could contribute to basal hyperinsulinemia. 3) Under conditions of hyperinsulinemia and falling plasma glucose, insulin secretion is rapidly suppressed in NIDDM (analogous to that in normal subjects studied during euglycemia. © 1985 by The Endocrine Society.
