Pancreatic lesions of small-obese mice (C57BL/6 J-ob/ob) with hyperglucagonemia

Male Small-obese mice (Small-ob) which derived from a C57BL/6 J-ob/ob mouse colony were examined histopathologically at 13-, 39-, and over 52-week-old. C57BL/6 J-ob mice (?/+: Non-ob, ob/ob: Ob) were studied as controls. In Small-ob mice, plasma glucagon concentration was higher than that of the Ob mice (this difference was highly significant), and serum levels for insulin was within normal limits. Microscopically, hypertrophy and hyperplasia of the islets of Langerhans were found only in the pancreas of Ob mice. The increase in the number of A-cells and the decrease in the number of B-cells were revealed immunohistochemically in the islets of Small-ob mice. These changes were more severe with advance of age. In the aged Small-ob mice, perivascular and periductular cell infiltration were found, but inflammatory change of islet tissue was not confirmed in any animals examined. Diabetic symptoms in Small-ob mice seems to stem from the disparity in insulin/glucagon (I/G) ratio associated with hyperglucagonemia which result from increased number of A-cells of pancreatic islets.