Fasting induces impairment of gastric mucosal integrity in non-insulin-dependent diabetic (db/db) mice

Background: Although diabetic patients often have gastrointestinal complica tions, the gastric mucosal function in diabetes has not been well documente d. Aim: To investigate the effect of fasting on the gastric mucosa in C57BL/Ks J-db +/+ db (db/db) mice, genetically non-insulin-dependent diabetic animal s. Methods: Blood glucose levels, gastric mucosal morphology, and the amount o f gastric mucin were examined before and after 18 h of fasting with free ac cess to water in db/db mice and their non-diabetic littermates (db/m). Results: Although 18 h of fasting reduced the blood glucose levels of both db/db and db/m mice, fasting decreased the amount of gastric adherent mucin and caused haemorrhagic gastric lesions only in db/db mice. After fasting, oral administration of ethanol induced much more severe gastric damage in db/db than in db/m mice. The above fasting-induced gastric damage such as h aemorrhagic lesions, loss of the mucin, and the increased sensitivity to et hanol worsened as the duration of diabetes became longer. Glucose ingestion in drinking water during the fasting counteracted the fall in blood glucos e and prevented the decrease in the amount of gastric mucin and the formati on of gastric mucosal lesions in db/db mice. Conclusion: These findings indicate that fasting-induced glucose deficit ca uses gastric mucosal lesions and increases the susceptibility of gastric mu cosa to noxious agents owing to the loss of mucus glycoprotein in db/db mic e. Prolonged diabetes is likely to augment the severity of fasting-induced impairment of the gastric mucosal function.