AJP - Gastrointestinal and Liver Physiology, Vol 270, Issue 1 163-G170, Copyright © 1996 by American Physiological Society

ARTICLES

Insulin inhibits secretin-stimulated pancreatic bicarbonate output by a dose-dependent neurally mediated mechanism

S. M. Berry and A. S. Fink
Department of Surgery, University of Cincinnati Medical Center, Ohio, USA.

Although previous reports suggest interactions between endocrine and exocrine pancreas, insulin's effect on pancreatic exocrine function remains unclear. Chronic pancreatic fistulas were created in six dogs with innervated INN and five dogs with denervated (DEN) pancreata; these animals were studied using the euglycemic, hyperinsulinemic clamp technique. After a 30-min unstimulated period, both groups received a 60-min 1.5 mU.kg-1.min-1 insulin (clamp) or vehicle (control) infusion. Intravenous secretin was then initiated at 16 ng.kg-1.h-1; the secretin dose was doubled every 30 min until 125 ng.kg-1.h-1 was achieved. These studies were then repeated in INN animals during infusion of a 10 micrograms.kg-1.h-1 atropine background. Finally, INN animals underwent a similar unstimulated period followed by a 1.25 mU.kg-1.min-1 insulin (clamp) or vehicle (control) infusion. after 60 min, a 64 ng.kg-1.h-1 secretin infusion was initiated. Insulin infusion was then increased by 0.25 mU.kg-1.min-1 at 30-min intervals until 2.0 mU.kg-1.min-1 was reached. Unstimulated (0-30 min) serum glucose and insulin levels and pancreatic bicarbonate and protein outputs did not differ between groups. Clamp (30-90 min) and stimulated (90-210 min) insulin were each significantly elevate in clamp groups (81.9 +/- 2.4 vs. 7.0 +/- 0.3 microU/ml, P < 0.001); glucose and bicarbonate were unchanged. Protein outputs during clamp (64 +/- 9 vs. 24 +/- 6 mg/10 min; P < 0.05) and secretin-stimulated (52 +/- 9 vs. 29 +/- 3 mg/10 min; P < 0.05) periods were diminished by atropine but were unaffected by insulin. Secretin-stimulated (90-210 min) bicarbonate output was diminished by insulin (0.03 +/- 0.01 vs. 0.31 +/- 0.05 meq/10 min; P < 0.003) in INN but not DEN animals; this effect was partially reversed by atropine. Dose-response studies demonstrated a threshold for insulin's inhibitory actions between 1.5 and 1.75 mU.kg-1.min-1. These data provide further evidence for exocrine-endocrine regulatory interactions and suggest that insulin may influence secretin's stimulation of ductal cell secretion by a mechanism that is at least partially cholinergic in character.