Kazumasa Nakama

Spontaneous diabetes-like syndrome in WBN/KOB rats.

SummarySpontaneous hyperglycemia, glycosuria, hypoinsulinemia, and glucose intolerance were observed in some WBN/Kob rats, at about 9 months of age, and in all at the age of 17 months. Females did not present this pathology. Histopathologic examination of the pancreas revealed severe changes in male rats at the age of 3 months. Between 3 and 6 months of age a distinct infiltration of inflammatory cells was found around islets and among adjacent acinar cells. At the same time, marked fibrosis was seen around the pancreatic ducts and blood vessels. With advancing age the fibrous tissue gradually invaded extensive areas of the pancreas where also the islets became involved in fibrotic degeneration. At 17 months of age and later, an obvious decrease in islet number and size (less than 50 µ in diameter) was observed, even in relatively unaffected areas of the organ. Frequent bilateral cataracts began to appear at about 15 months of age. Opacities were first observed in the periphery of the lens, then increased rapidly in intensity and extended centripetally. Nineteen-month-old male rats were hypersensitive to exogenous insulin, but showed no significant decrease in blood glucose level when treated with oral tolbutamide. These results suggest that these rats suffered from a decreased insulinogenic response.

Wbn/Kob rats

SummaryChronic pancreatitis-like lesions are observed in 100% of male Wistar Bonn/Kobori rats. At 3 mo of age, histopathologic examinations of the pancreas revealed a distinct infiltration of inflammatory cells with interstitial edema in the acini. At the same time, periductal and interstitial fibrosis and adenomatous hyperplasia of the ductular epithelium were observed. Extensive fibrotic exudation developed rapidly with age, and irregular destruction of the parenchyma was noted. The only abnormality, prior to the appearance of glycosuria, that could be detected clinically was lower levels, compared to Wistar rats, of BT-PABA excreted in the urine after oral ingestion. These lower levels indicate a decrease in enzyme secretion in WBN/Kob rats.Ultrastructural observations in histologically normal areas at 2 mo of age showed a swelling of mitochondria, indicating that ischemia was associated with the early pancreatic lesions. Serial pancreatographies were performed at 2–8 mo of age. Irregular widenings of the main pancreatic duct and dilations of the smaller ducts were observed already at 2 mo of age, suggesting a stasis of pancreatic juice in the early stages of the disease. It seems that male WBN/Kob rats are a useful model of human chronic pancreatitis, with an unknown mechanism regulated by the sex hormones.

Renal lesions in a strain of spontaneously diabetic WBN/KOB rats

SummaryIn WBN/Kob strain rats, only males spontaneously develop hyperglycemia, glycosuria, hypoinsulinemia and glucose intolerance from about nine months of age. The kidneys of male rats of this strain were histopathologically studies to evaluate the changes which appeared as complications of diabetes mellitus. Thickening of the basement membrane, increase of the mesangial matrix and fibrin-cap lesions were noted in the glomeruli. Armanni-Ebstein degeneration was occasionally found in the tubules. Linear deposition of plasma components such as IgG and albumin in the basement membrane of the glomeruli, tubules and Bowman’s capsule characterized the immunohistological pattern. These findings are similar to the findings in diabetic nephropathy in humans. Since the onset of diabetes mellitus in the strain is slow and symptoms are generally mild, insulin administration is usually not necessary for survival. This strain, therefore, appears to be an important animal model for the study of complications of diabetes in humans.