Alterations in duodenal bicarbonate secretion and mucosal susceptibility to acid in diabetic rats

Background & Aims: The gastroduodenal mucosal susceptibility to ulcerogenic stimuli increases in diabetic conditions, but the mechanism is unknown. The aim of this study was to investigate alterations in duodenal HCO3- secretory response in diabetic animals. Methods: The experiments were performed in rats treated with streptozotocin (70 mg/kg intraperitoneally) after 1-6 weeks of diabetes, when blood glucose levels were >300 mg/dL. HCO3- secretion was measured in the proximal duodenal loop of rats that were under urethane anesthesia using a pH-stat method. Results: The duodenal HCO3- secretion induced by mucosal acidification was decreased in streptozotocin-treated rats depending on the duration of diabetes. The HCO3- secretion was also decreased in response to 16,16-dimethyl prostaglandin E(2), vasoactive intestinal polypeptide, or vagal electrical stimulation. Acid load in the duodenum produced extensive damage in 5-6-week diabetic rats, although the same treatment caused only slight damage in the normal rat duodenum. Such alterations in the duodenal HCO3- secretory and ulcerogenic responses in diabetic rats were partially restored by daily injection of insulin. Conclusions: The results suggest that streptozotocin-diabetic conditions impair the duodenal HCO3- secretion in rats, possibly as a result of decreased sensitivity of the epithelial cell and dysfunction of neuronal pathway, thereby increasing the mucosal susceptibility to acid injury in the duodenum.