Insulin inhibits secretin-stimulated pancreatic bicarbonate
secretion by a dose-dependent, neurally-mediated mechanism.
Berry, Scott M., and Aaron S. Fink.
Departments of Surgery, University of Cincinnati Medical Center and
Cincinnati VA Medical Center, Cincinnati, OH, and Emory University
School of Medicine, Atlanta, GA and the Atlanta VA Medical Center,
Decatur, GA
APStracts 2:0162G, 1995.
Although previous reports suggest interactions between the endocrine
and exocrine pancreas, insulin's effect on pancreatic exocrine
function remains unclear. Chronic pancreatic fistulae 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/min insulin (clamp) or
vehicle (control) infusion. Intravenous secretin was then initiated
at 16 ng/kg/hr; the secretin dose was doubled every 30 min until 125
ng/kg/hr was achieved. These studies were then repeated in INN
animals during infusion of a 10 [mu]g/kg/hr atropine background.
Finally, INN animals underwent a similar unstimulated period followed
by a 1.25 mU/kg/min insulin (clamp) or vehicle (control) infusion.
After 60 min, a 64 ng/kg/hr secretin infusion was initiated. The
insulin infusion was then increased by 0.25 mU/kg/min at 30 min
intervals until 2.0 mU/kg/min 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) insulins were significantly elevated in clamp
groups (81.9 +/- 2.4 vs. 7.0 +/- .3 [mu]U/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 (.03 +/- .01
vs. 0.31 +/- .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/min. 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 which is at least partially cholinergic in
character.
Received 24 January 1995; accepted in final form 21 July 1995.
APS Manuscript Number G33-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.