Histopathological changes in the pancreas from a spontaneous hyperglycemic cynomolgus monkey

Abstract

Morphological and immunohistochemical examinations were carried out on the pancreas of a hyperglycemic 5-year-old male cynomolgus monkey. Body weight gradually decreased from 6 months before termination, accompanying a slight reduction in food consumption and anorexia for the last 2 days. The blood glucose level was markedly elevated when examined at termination. Histopathologically, in the exocrine pancreas, diffuse hyperplasia of centroacinar and intercalated duct cells and diffuse atrophy of acinar cells with sporadic apoptosis were observed, although most centroacinar and intercalated duct cells were proliferating cell nuclear antigen (PCNA)-positive in both the present case and age-matched control animals. In the endocrine pancreas, the islets tended to be hypertrophic, with an increase in insulin-positive cells in comparison with the age-matched control animals. PCNA-positive cells also tended to increase in the islets, although positive cells for phospho-histone H3, a marker for mitotic cells, were not detected in the endocrine and exocrine pancreas. Moreover, neither inflammation nor amyloidosis was noted in the islets. In conclusion, the present case probably suffered from early-stage type 2 diabetes mellitus, and it provides fundamental information concerning pancreatic histopathology under insulin-related derangement in monkeys.

Keywords: centroacinar and intercalated duct cell hyperplasia; cynomolgus monkey; pancreas; pontaneous diabetes mellitus; β-cell hyperplasia.

Fig. 1.

Histological appearance of the pancreas. Normal pancreas from the comparative animals (a, b). Diffuse hyperplasia of the centroacinar and intercalated duct cells and diffuse atrophy of acinar cells in the present case (c, d). HE stain. Bar = 500 μm (a, c), 100 μm (b, d).

Fig. 2.

Immunohistochemistry of the pancreas. The number of insulin-positive cells in the present case (c, d) is greater than that in the comparative animals (a, b). In PCNA immunohistochemistry, the number of positive cells (arrows) in the islets from the present case (f) tends to increase in comparison with that in the comparative animals (e), whereas most centroacinar and intercalated duct cells are PCNA-positive in both the present case (f) and the comparative animals (e). In CAS3 immunohistochemistry, positive cells are sporadically seen in the exocrine pancreas from the present case (g). Bar = 500 μm (a, c), 100 μm (b, d, e, f) 25 μm (g).

Fig. 3.

Ultrastructure of islets from the present case. No distinct abnormal changes are seen in the component cells. Bar = 5 μm.