DEFECTIVE INSULIN AND GLUCAGON-SECRETION IN ISOLATED-PERFUSED PANCREASES OF DIABETIC WBN KOB RATS/

To elucidate the pathophysiology of diabetes mellitus in male WBN/Kob rats, we performed pancreatic perfusion experiments and histopathologi cal studies. Intraperitoneal glucose tolerance tests showed a diabetic pattern in 12-month-old WBN/Kob rats. In perfused pancreata of WBN/Ko b rats, both the first and the second phases of insulin secretion in r esponse to a 16.7 mM glucose challenge were markedly reduced compared with those in age-matched Wistar rats (p < 0.01, respectively). Furthe rmore, the insulin secretion rate in response to glucopenia (1.4 mM) w as significantly higher (p < 0.05) and the decrement in insulin secret ion 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 to glucopenia was also significantly lower in WBN/Kob rats than in controls (p < 0.0 1). 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. Hi stopathological examination revealed widespread disappearance of acina r cells and islets, inflammatory changes, and marked fibrosis in the p ancreata of WBN/Kob rats. Immunohistochemical studies showed decreased numbers of B cells in the islets of WBN/Kob rats. These findings sugg est that this WBN/Kob rat strain is a useful model for studying not on ly pathogenesis, but also pathophysiology, i.e., defective hormonal se cretion, in some types of human diabetes mellitus.