2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced impairment of glucose-stimulated insulin secretion in isolated rat pancreatic islets.

We have explored the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administration on the secretory function of isolated rat pancreatic islets. Twenty-four hours after TCDD administration (1 microg/kg b.w., i.p.), rats showed no significant differences in plasma glucose, insulin, triglycerides and leptin levels whereas plasma-free fatty acids were significantly increased with respect to untreated controls. In isolated islets, DNA and protein content were unchanged, whereas insulin content was significantly decreased in TCDD-treated rats. Incubation with different concentrations of glucose demonstrated a significant impairment of glucose-stimulated insulin secretion in islets isolated from TCDD-treated rats, whereas insulin release was better preserved upon alpha-ketoisocaproate stimulation. A significant reduction of [3H]-2-deoxy-glucose uptake was observed in pancreatic tissue of TCDD-treated rats, whereas no significant reduction in GLUT-2 protein levels was detectable by immunoblotting in islets from TCDD-treated rats. We concluded that low-dose TCDD could rapidly induce significant alterations of the pancreatic endocrine function in the rat.