Modulation of Insulin Secretion by Insulin and Glucose in Type II Diabetes Mellitus

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 ...