Perturbation of pancreatic islet function in glucose-infused rats

The secretory behavior of insulin- and glucagon-producing cells was found to be perturbed in isolated perfused pancreases removed from rats infused with hypertonic solutions of glucose for 48 hours. The anomalies included a high basal release of insulin and a paradoxical increase in insulin output and decrease in glucagon release in response to a fall in D-glucose concentration. Likewise, in isolated islets prepared from the glucose-infused rats, L-arginine or theophylline stimulated insulin release at a low ambient concentration of D-glucose, at variance with the situation found in islets removed from normal rats. These secretory perturbations could not be attributed to any obvious defect in either the transport of D-glucose into islet cells or its further utilization and oxidation, but coincided with the abnormal accumulation of glycogen in the B-cell. It is proposed that the latter anomaly may play a role in the altered dynamics of insulin release found in animals or patients with long-term hyperglycemia.