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Current Topics in Pharmacology   Volumes    Volume 11  Issue 2
Alterations in gastric mucosal homeostasis under diabetic conditions
Koji Takeuchi, Roman Korolkiewicz, Kimihito Tashima
Pages: 45 - 61
Number of pages: 17
Current Topics in Pharmacology
Volume 11  Issue 2

Copyright © 2007 Research Trends. All rights reserved


Streptozotocin-induced diabetic rat is an accepted model of insulin-dependent diabetes. Using this model, we examined the influence of diabetes on mucosal vulnerability to ulcerogenic stimuli and the healing of gastric lesions as well as gastro-duodenal functions. Diabetic conditions increased the mucosal vulnerability of the stomach to food deprivation, topical application of bile acids, and ischemia/reperfusion, resulting in hemorrhagic damage, and this response occurred depending on the duration of diabetes. Diabetes also delayed the healing of 0.6 M HCl-induced gastric lesions, in association with a down-regulation of the expression of growth factors such as basic fibroblast growth factor and insulin-like growth factor. Furthermore, diabetes altered various functions in these tissues, such as the impairment of gastric mucosal blood in response to acid back-diffusion following epithelial injury, the increase in peptone-stimulated acid secretion and the impaired duodenal bicarbonate response to mucosal acidification, and the functional abnormalities are partly attributable to neuronal dysfunction involving vagus nerves and capsaicin-sensitive afferent neurons. All these alterations observed in STZ-diabetic rats were insulin-dependent and significantly reversed by the daily administration of zinc insulin. These results point towards another causative factor in the battery of aggressive mechanisms evoking mucosal damage and delayed healing of ulcers in the course of diabetes, involving the impairment of mucosal blood flow, alteration of acid and bicarbonate secretory responses as well as dysregulation of growth factor expression. Overall, the results underlay the importance of the early insulin regimen in order to prevent diabetic gastrointestinal complications.

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