Comparison of the inhibitory effect of insulin and hypoglycemia on insulinsecretion in humans

Although both insulin and hypoglycemia are known to inhibit endogenous insu lin secretion, their potency to suppress insulin secretion has not been dir ectly compared thus far. The serum C-peptide concentration was measured dur ing 28 euglycemic and 28 stepwise hypoglycemic (4.1, 3.6, 3.1, and 2.6 mmol /L) clamp experiments using either a law-rate (1.5 mU . min(-1) . kg(-1)) o r high-rate (15.0 mU . min(-1) . kg(-1)) insulin infusion. The experiments lasted 6 hours and were performed in 28 lean healthy men. During bath the e uglycemic and hypoglycemic clamps, serum insulin was approximately 40-fold higher during the high-rates versus tow-rate insulin infusion (euglycemia, 24,029 +/- 1,595 v 543 +/- 34 pmol/L; hypoglycemia, 23,624 +/- 1,587 v 622 +/- 32 pmol/L). Under euglycemic conditions, serum C-peptide decreased from 0.54 +/- 0.04 to 0.41 +/- 0.05 nmol/L during the low-rate insulin infusion (P < .05) and from 0.55 +/- 0.07 to 0.27 +/- 0.09 nmol/L during the high-r ate insulin infusion (P < .001). Under hypoglycemic conditions, serum C-pep tide decreased from 0.50 +/- 0.03 to 0.02 +/- 0.01 nmol/L during the low-ra te insulin infusion (P < .001) and from 0.46 +/- 0.07 to 0.02 +/- 0.01 nmol /L during the high-rate insulin infusion (P < .001). In the euglycemic clam p condition, the high-rate insulin infusion reduced the C-peptide concentra tion more than the low rate insulin infusion (P < .05). Independent of the rate of insulin infusion, the decrease in C-peptide was distinctly more pro nounced during hypoglycemia versus euglycemia (P < .001). These data indica te that insulin inhibits insulin/C-peptide secretion in a dose dependent ma nner. Hypoglycemia is a much stronger inhibitor of insulin secretion than i nsulin itself. Copyright (C) 2000 by W.B. Saunders Company.