Experimental diabetic diarrhea in rats: Intestinal mucosal denervation hypersensitivity and treatment with clonidine

Abstract

Diarrhea in streptozocin-induced chronically diabetic rats is caused by an impaired adrenergic regulation of intestinal fluid and electrolyte transport. Stimulation of α2-adrenergic receptors on enterocytes normally promotes NaCl absorption and inhibits HCO3 secretion. The purpose of this study was to determine (a) if adrenergic denervation of intestinal mucosa in chronically diabetic rats alters postsynaptic receptor response, and (b) if the α2-adrenergic agonist clonidine could correct observed fluid malabsorption. Mucosal norepinephrine stores, a measure of adrenergic tone, were markedly reduced in diabetic rats compared with nondiabetic littermates. In vitro, short-circuit current changes to exogenously added l-epinephrine were significantly greater in diabetics, suggesting that denervation hypersensitivity was due to increased numbers of postsynaptic α2-adrenergic receptors. In vivo loop studies demonstrated net fluid secretion in the ileum and colon of diabetics. In diabetics, clonidine reversed the secretion to absorption, but it had no effect on fluid absorption in controls. We conclude that diabetic diarrhea in streptozocin-induced chronically diabetic rats is (a) due to impaired adrenergic regulation of mucosal ion transport, (b) accompanied by a postsynaptic denervation hypersensitivity that can be reversed by clonidine, and (c) accompanied by net intestinal fluid secretion that can be effectively reversed with clonidine.