The effect of epinephrine on insulin and glucagon secretion from the endotoxic rat pancreas.

Abstract

This study determined whether in vivo endotoxin treatment alters the ability of epinephrine to inhibit immunoreactive insulin (IRI) secretion or to stimulate immunoreactive glucagon (IRG) secretion from the in vitro perfused rat pancreas preparation. Insulin and glucagon secretion were measured from pancreases obtained from control and endotoxin-treated rats. The pancreases were perfused with 240 mg/dl glucose in the presence and the absence of 13.6 nM epinephrine. The absolute ability of epinephrine to inhibit glucose-induced IRI secretion was similar for both "control" and "endotoxic" pancreases. However, since endotoxic pancreases hypersecrete insulin, the relative ability of epinephrine to inhibit insulin secretion was reduced in endotoxic compared with control pancreases. Epinephrine did not appreciably alter IRG secretion in control pancreases. However, epinephrine prevented a progressive decrease in IRG secretion in endotoxic pancreases. The results suggest that the relative inability of epinephrine to inhibit the excess insulin secretion due to endotoxin treatment contributes to endotoxin-induced hyperinsulinemia. Furthermore, the additional observation that epinephrine supported glucagon secretion in the endotoxic pancreas in the face of high glucose levels suggests epinephrine may play a deleterious role with respect to glucose homeostasis during endotoxicosis. The results provide a partial mechanism to explain endotoxin-induced hyperinsulinemia and also demonstrate a possible role for epinephrine with regard to the production of elevated glucagon levels during endotoxicosis.