Impaired stimulation of intestinal glucose absorption via hepatoenteral nerves in streptozotocin-diabetic rats

In an ex situ organ perfusion system, that of the isolated nonrecirculating joint perfusion of rat small intestine and liver, insulin infused into the portal vein increased intestinal glucose absorption. This insulin action a gainst the bloodstream can be blocked by TTX, indicating a propagation of t he insulin signal via hepatoenteral nerves, which conforms with previous st udies with atropine and carbachol. Insulin action could also be mimicked by dibutyryl cAMP (DBcAMP) acting directly on the absorptive enterocytes. Bec ause autonomic neuropathy is a common late complication of diabetes mellitu s, the possible impairment of these nerves in the diabetic state was studie d in streptozotocin-diabetic rats. In the isolated joint intestine-liver pe rfusion, glucose was applied as a bolus into the lumen; its absorption was measured in the portal vein. In 5-day diabetic as well as in control rats, portal insulin, arterial carbachol, and arterial DBcAMP increased intestina l glucose absorption. In 3-mo diabetic rats portal insulin and arterial car bachol failed to stimulate glucose absorption, whereas arterial DBcAMP stil l did so, indicating an undisturbed function of the absorptive enterocytes. The lack of an effect of portal insulin and arterial carbachol and the unc hanged action of DBcAMP in the chronically diabetic rats indicated that the signaling chain via the hepatoenteral nerves was impaired, which is in lin e with a diabetic neuropathy.