Impaired insulin but normal pentagastrin effect on gastric acid secretion in diabetic rats: a role for nitric oxide

Abstract

Significant changes in gastrointestinal function, decreased gastric secretion and motility in particular, are often observed in patients with chronic diabetes. The mechanisms leading to those remain unclear. In these studies we evaluated the gastric acid secretory response to insulin and pentagastrin in normal Wistar and streptozotocin diabetic rats. We also sought to determine the role of nitric oxide (NO) in this process. The animals were anesthetized with sodium pentobarbital. Warm saline was perfused through a polyethylene tube placed in the oesophagus and collected from the duodenum at 10 min intervals. Following a 50 min equilibration period, a bolus intra-jugular infusion of insulin (4.0 U/kg), 2-deoxyglucose (200 mg/kg) or pentagastrin 4.0 (ug/kg) was started and samples of the gastrointestinal perfusate were collected for an additional 80 min. Insulin-stimulated acid secretion peaked 60 min after bolus infusion in normal animals; a response that was significantly decreased in the diabetic rats. Similarly, 2-deoxyglucose-induced glucopenia increased gastric acid secretion to a lower extent in diabetic versus normal rats. The stimulatory response to pentagastrin was prompt and essentially equal in normal and diabetic animals. However, when hypoglycemia was prevented by glucose infusion, insulin did not stimulate gastric acid secretion in normal rats. Further, glucose infusion in these animals actually enhanced the secretory response to pentagastrin. Nitro-L-arginine methyl ester (L-NAME 20 mg/kg i.v.), an inhibitor of NO synthetase, also prevented the secretory response to insulin but not to pentagastrin. Preinfusion of arginine (100 mg/kg i.v.) in diabetic rats restored the gastric secretory response to insulin toward that of normal animals. We conclude that the gastric acid secretory response to insulin, but not to pentagastrin, is decreased in diabetic animals, that this response may operate through a NO mediated mechanism possibly set in motion by central nervous system glucopenia and that this NO-mediated mechanism is attenuated in diabetes.