Defective insulin and glucagon secretion in isolated perfused pancreata of diabetic WBN/Kob rats

To elucidate the pathophysiology of diabetes mellitus in male WBN/Kob rats, we performed pancreatic perfusion experiments and histopathological studies. Intraperitoneal glucose tolerance tests showed a diabetic pattern in 12-month-old WBN/Kob rats. In perfused pancreata of WBN/Kob rats, both the first and the second phases of insulin secretion in response to a 16.7 mM glucose challenge were markedly reduced compared with those in age-matched Wistar rats (p < 0.01, respectively). Furthermore, the insulin secretion rate in response to glucopenia (1.4 mM) was significantly higher (p < 0.05) and the decrement in insulin secretion was significantly lower (p < 0.05) in WBN/Kob rats. The decrement in glucagon secretion with 16.7 mM glucose was significantly blunted (p < 0.001), and the glucagon secretion rate in response toglucopenia was also significantly lower in WBN/Kob rats than in controls (p < 0.01). Although insulin secretion in response to 10 mM arginine was also moderately reduced in WBN/Kob rats (p < 0.05), the glucagon secretion rates in response to 10 mM arginine were similar in the two groups. Histopathological examination revealed widespread disappearance of acinar cells and islets, inflammatory changes, and marked fibrosis in the pancreata of WBN/Kob rats. Immunohistochemical studies showed decreased numbers of B cells in the islets of WBN/Kob rats. These findings suggest that this WBN/Kob rat strain is a useful model for studying not only pathogenesis, but also pathophysiology, i.e., defective hormonal secretion, in some types of human diabetes mellitus.