QUANTITATIVE IMMUNOHISTOCHEMICAL CHANGES IN THE ENDOCRINE PANCREAS OFNONOBESE DIABETIC (NOD) MICE

The nonobese diabetic (NOD) mouse is an animal model that shares a num ber of clinical, genetic, and immunologic characteristics with human i nsulin-dependent diabetes mellitus. Since little is known about the mo rphometric cell profiles in the endocrine pancreas of these NOD animal s, it was of interest to assess their changes in morphometry within th e pancreatic islet cell types during two stages of this syndrome, Pred iabetic (6-week-old) and diabetic (16-week-old) NOD female mice, as we ll as normal C57BL/6 female mice (15 weeks old), were used. Light micr oscopic immunocytochemical and morphometric methods were employed to s tudy the endocrine cell populations. The immunoperoxidase technique fo r the identification of insulin, glucagon, somatostatin, and pancreati c polypeptide, as well as the point-counting method, was used on seria l sections of pancreas tissue. Compared to those of normal and prediab etic mice, pancreata from diabetic animals showed a decrease in both t he number of islets and the volume density of the endocrine component. Analysis of islet tissue revealed a significant diminution of B-cell volume density, as well as an increased A-, D-, and PP-cell volume den sity. A parallel variation in the number of B and non-B cells was also found. In addition, when the total pancreatic tissue surface was take n as reference, the fractional area occupied by all the different type s of islet cells was seen to be diminished in a variable fashion, We c onclude that the diabetic syndrome of NOD mice not only severely affec ts the B-cell mass, but also causes marked changes in the non-B endocr ine-cell populations.