[The effect of theophyllin on small intestinal structure and function of the diabetic rat (author's transl)]

In order to obtain some information about the role of cAMP in the regulation of cell turnover of the intestinal mucosa it was interesting to investigate whether chronic pharmacologically induced changes in the cellular cAMP levels could cause alterations in mucosal growth in the case of a well defined animal modell, involving increased cell proliferation rate, such as chronic experimental diabetes mellitus of the rat. Since it has been suggested that cAMP levels on the one hand are low in cell division and increased cAMP levels on the other hand inhibit cell division, the aim of the study was to induce a suppression of the cell proliferation rate in the intestinal mucosa by chronic theophyllin application, a well known PDE-inhibitor. The following results could be obtained: Chronic theophyllin application induces a hyperplastic alteration of the small intestinal mucosa of the rat, which is similar to that observed in diabetes mellitus. In diabetic animals theophyllin causes a further increase in hyperplasia. The morphological alterations of the intestinal mucosa are more pronounced than the functional changes. In experimental diabetes mellitus the radioimmunologically determined cAMP level in the intestinal mucosa is rather low. Chronic theophyllin application alone or in combination with experimental diabetes mellitus was unable to increase the cAMP-level continuously. This could be a result of an adaptive change of the cAMP regulating enzyme system. Therefore theophyllin induced mucosal alterations are probably due to systemic effects of this drug.