Insulin inhibits secretin-induced pancreatic bicarbonate output via cholinergic mechanisms

• Published in: Pancreas Vol. 24; no. 4; p. 380
• Main Authors: Howard-McNatt, Marissa, Simon, Timothy, Wang, Yuanhong, Fink, Aaron S
• Format: Journal Article
• Language: English
• Published: United States 01.05.2002
• Subjects: Animals; Bethanechol - pharmacology; Bicarbonates - metabolism; Blood Glucose; Cholinergic Agonists - pharmacology; Dogs; Drug Interactions; Glucose Clamp Technique; Hypoglycemic Agents - blood; Hypoglycemic Agents - pharmacology; Insulin - blood; Insulin - pharmacology; Pancreas - drug effects; Pancreas - metabolism; Parasympathomimetics - pharmacology; Secretin - pharmacology
• ISSN: 0885-3177
• DOI: 10.1097/00006676-200205000-00009

Exogenous insulin inhibits secretin-stimulated pancreatic bicarbonate output via a dose-dependent mechanism; this effect is prevented by pancreatic denervation. To investigate possible cholinergic mediation, we examined the effect of bethanechol on secretin-stimulated pancreatic secretion during euglycemic, hyperinsulinemic clamp. In four dogs with chronic pancreatic fistulas, euglycemic, hyperinsulinemic clamp (1.25 mU/kg/min) was begun after a 30-minute basal period; computer-assisted glucose administration maintained euglycemia. Control studies were performed with volume-matched and rate-matched vehicle infusion. After 1 hour, secretin infusion was begun at a dosage of 16 ng/kg/h; the dose was doubled every 30 minutes. The studies were then repeated during background bethanechol infusion (90 microg/kg/h) begun 30 minutes after clamp initiation. Pancreatic juice was analyzed for bicarbonate and protein; serum samples were analyzed for glucose and insulin. Exocrine outputs and serum glucose and insulin levels did not differ in the basal period. Insulin levels were significantly elevated during the euglycemic, hyperinsulinemic clamp (62 microU/mL versus 12 microU/mL; p < 0.01); glucose levels did not differ. As before, secretin-induced bicarbonate output was inhibited by euglycemic, hyperinsulinemic clamp. The inhibitory effect of insulin was reversed by bethanechol. Despite the euglycemic, hyperinsulinemic clamp, secretin-induced bicarbonate output was potentiated by bethanechol at higher secretin doses (p < 0.05). These data confirm that cholinergic mechanisms mediate insulin's inhibition of secretin-induced pancreatic bicarbonate output.