IMPAIRED INSULIN BUT NORMAL PENTAGASTRIN EFFECT ON GASTRIC-ACID SECRETION IN DIABETIC RATS - A ROLE FOR NITRIC-OXIDE

Significant changes in gastrointestinal function, decreased gastric se cretion and motility in particular, are often observed in patients wit h chronic diabetes. The mechanisms leading to those remain unclear. In these studies we evaluated the gastric acid secretory response to ins ulin and pentagastrin in normal Wistar and streptozotocin diabetic rat s. We also sought to determine the role of nitric oxide (NO) in this p rocess. The animals were anesthetized with sodium pentobarbital. Warm saline was perfused through a polyethylene tube placed in the oesophag us 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 f or an additional 80 min. Insulin-stimulated acid secretion peaked 60 m in after bolus infusion in normal animals; a response that was signifi cantly decreased in the diabetic rats. Similarly, 2-deoxyglucose-induc ed glucopenia increased gastric acid secretion to a lower extent in di abetic versus normal rats. The stimulatory response to pentagastrin wa s 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 inf usion in these animals actually enhanced the secretory response to pen tagastrin. Nitro-L-arginine methyl ester (L-NAME 20 mg/kg i.v.), an in hibitor of NO synthetase, also prevented the secretory response to ins ulin but not to pentagastrin. Preinfusion of arginine (100 mg/kg i.v.) in diabetic rats restored the gastric secretory response to insulin t oward that of normal animals. We conclude that the gastric acid secret ory response to insulin, but not to pentagastrin, is decreased in diab etic animals, that this response may operate through a NO mediated mec hanism possibly set in motion by central nervous system glucopenia and that this NO-mediated mechanism is attenuated in diabetes. (C) 1997 E lsevier Science Ireland Ltd.