Role of Acid Back-diffusion in the Formation of Mucosal Ulceration and Its Treatment with Drugs in Diabetic Rats

Abstract

Abstract We have studied the role of acid back-diffusion in the formation of gastric mucosal ulceration and its treatment with several drugs in streptozotocin-induced diabetic rats. After vagotomy, the stomach of 1–8 week-old diabetic rats and age-matched control rats were irrigated with acid solutions of graded concentrations (50–150 mm HCl) for 1 or 3 h. A marked increase in acid back-diffusion and in haemorrhagic ulceration was found in diabetic rats. The extent of acid back-diffusion and the severity of mucosal ulceration were dependent on the concentration and the time of contact of acid solutions with the gastric mucosa. A high correlation (r = −0·9227) between acid back-diffusion and mucosal ulceration was found in 3-h acid-irrigated diabetic rats. In the 2-week diabetic rat, intragastric cimetidine (300 mg kg−1) or NaHCO3 (52 mg kg−1) significantly (P < 0·05) reduced both acid back-diffusion and haemorrhagic ulcer formation, while atropine (1·0 mg kg−1) or bupivacaine (0·5%, 0·4 mL/rat) was ineffective. High blood glucose levels in diabetic rats were not influenced by these agents. Acid back-diffusion and ulceration in the diabetic rat were markedly reduced by daily administration but not single injection of insulin (50 units kg−1, s.c.). Taken together, in the early stage of diabetes development, chronic insulin deficiency rather than nerve degeneration or hyperglycaemia may be responsible for the disruption of mucosal barriers. It is concluded that acid back-diffusion played an important role in the formation of acute haemorrhagic ulceration that can be inhibited by intragastric cimetidine, NaHCO3 or daily injection of insulin.