Studies on gastrointestinal tract functional changes in diabetic animals.

Diarrhea and constipation are frequently reported gastrointestinal complications in diabetic patients. These disorders seem to be the consequence of altered innervations of a receptor system in the gastrointestinal tract in diabetes. We investigated the functional changes of cholinergic and beta-adrenergic receptor activities in rat ileum tissue after 8 weeks of control and streptozotocin (STZ)-induced diabetes in rats. Functional changes with different agonists were observed in diabetes: In diabetic rat ileum, carbachol increased the maximal contraction without changing pD2 values, whereas with acetylcholine, no changes were observed in the maximal contractile (Emax) response and pD2 values in diabetes were comparable with controls. With the beta-adrenoceptor agonists isoproterenol and salmeterol, decreased maximal relaxation responses were observed in 8-week diabetic rat ileums as compared with age-matched controls. With isoproterenol, pD2 values were also decreased in diabetic ileum, although not with salmeterol. On the other hand, with the in vivo charcoal meal test, the percentage of transit was increased in diabetic mice. The antitransit percentage was significantly increased in diabetic mice with the muscarinic antagonist atropine and the beta 2-selective agonist salbutamol, as compared with age-matched control mice. Results obtained from these in vivo and in vitro studies indicate that gastrointestinal complications such as diabetic diarrhea may occur because of functional changes such as increased intestinal transit and decreased intestinal tone due to increased cholinergic and decreased beta-adrenergic receptor activities in diabetes mellitus.