Induction of EGFR tyrosine kinase in the gastric mucosa of diabetic rats

Diabetes mellitus is associated with spontaneous gastric mucosal injury and enhanced susceptibility of the mucosa to damaging agents. Little informati on is available about the biochemical changes that occur in the gastric muc osa of diabetes mellitus. Evidence is accumulating that tyrosine kinases, p articularly the EGF-receptor (EGFR), are involved in regulating a variety o f structural and functional properties of the gastric mucosa. The primary o bjectives of this investigation were to determine whether diabetes induces morphological changes in the gastric mucosa, and if so, whether these chang es are associated with alterations in EGFR tyrosine kinase. Diabetes-induce d changes in gastric mucosal morphology were also examined. Diabetes was in duced in 3- to 4-month-old male Fischer-344 rats by streptozotocin (STZ; 45 mg/kg; i.v.). Four weeks after induction of diabetes mellitus, the gastric mucosa of overnight-fasted rats was found to be slightly atrophic. A reduc tion in gastric mucosal thickness with deposition of fibrous tissue above t he muscularis layer was observed in the stomach of overnight-fasted diabeti c rats. These changes were associated with a marked stimulation in tyrosine kinase activity and protein expression of EGFR. The relative concentration s of several precursor forms of TGF-alpha in both membrane and cytosolic fr actions from the gastric mucosa of overnight-fasted diabetic rats were also found to be significantly above the corresponding controls. This suggests that endogenous TGF-alpha may play a critical role in regulating mucosal EG FR tyrosine kinase through a juxtacrine/paracrine mechanism.