EXOGENOUS INSULIN DOSE-DEPENDENTLY SUPPRESSES GLUCOPENIA-INDUCED GLUCAGON-SECRETION FROM PERFUSED RAT PANCREAS

To clarify the role of insulin in modulating the glucagon response to glucose concentration changes, we investigated the effects of exogenou s insulin (10 mU/mL, 100 mU/mL, and 3.3 U/mL) on responses to high glu cose (5.6 --> 16.7 mmol/L), low glucose (5.6 --> 1.4 mmol/L), and argi nine (10 mmol/L) stimulation using the perfused rat pancreas. Although glucagon levels were slightly suppressed by all of the exogenous insu lin concentrations tested for the initial few minutes at 5.6 mmol/L gl ucose, baseline levels were maintained thereafter. Glucagon responses to high or normal glucose concentrations were not altered, but glucope nia-induced glucagon secretion was significantly suppressed as compare d with that of controls (0.77 +/- 0.14 ng/min [10 mU/mL, n = 5], 0.55 +/- 0.14 ng/min [100 mU/mL, n = 5], 0.27 +/- 0.13 ng/min [3.3 U/mL, n = 5] v 1.38 +/- 0.20 ng/min [controls, n = 9], P < .05, respectively). The first phase of the glucagon response to arginine was potentiated (2.03 +/- 0.24 v 1.17 +/- 0.22 ng/min, P < .05) by 10 mU/mL exogenous insulin. The second phase of the glucagon response to arginine was sig nificantly suppressed in the presence of higher concentrations of exog enous insulin (1.16 +/- 0.23 ng/min [100 mU/mL], 0.96 +/- 0.08 ng/min [3.3 U/mL] v 1.57 +/- 0.17 ng/min, P < .05, respectively). These resul ts suggest that glucagon secretion is modified by the combined suppres sive effects of glucose and insulin, although it is mainly glucose tha t mediates glucagon secretion in the physiological glucose range. Gluc openia- or arginine-induced glucagon secretion is suppressed by insuli n. Copyright (C) 1995 by W.B. Saunders Company