Hyperglycemia in the NZB/NZW F₁ hybrid mouse

Abstract

Both the NZW and NZB mice exhibit an elevated fasting blood sugar level when compared to Swiss white mice. The NZB/NZW F1 hybrid mouse shows still a higher fasting serum glucose level than either of its parental strains. The elevated glucose level is noted very early in the animals' life, long before definitive signs or symptoms of pathology are evident, and remains elevated at least until the fortieth week of life, the last testing period in our series before sacrificing the aminals. There are two major peaking periods for the glucose levels, namely at 4-10 weeks of age and then again at 31-40 weeks of age. These age periods correspond to the very young animal and to the animal that is beyond its prime and most likely sick and near the end of its lifespan due to the animals' inherent disease processes. The NZB and NZB/NZW F1 hybrid succumb to their disease processes at approximately 8-10 months of age. The NZW usually lives until 18 months. The questions are raised: does the altered immunologic state in the NZB and/or the NZB/NZW F1 hybrid produce the elevated blood sugar levels and the pancreatic histopathology or is it the early hyperglycemic condition coupled with pancreatic pathology which are in some measure instrumental in producing the lesions discussed and observed, in the beginning of the three to four month period of age, in the various organs? Is there a relationship between the hyperglycemic condition and the immune state or are these independent phenomena in a genetically "mixed up" mouse?

Demonstration of Islet Cell Surface Antibodies in Sera of New Zealand Black Mice and Inhibitory Effect on Insulin Release

“…Fasting hyperglycemia has been described in NZB/NZW F1 mice at 4-10 and 3 1 -40 wk of age. 4 Our study showed that NZB mice were characterized by the elevation of plasma glucose concentration after the glucose load rather than by fasting hyperglycemia in accordance with a recent report on slow clearance of intravenous glucose in New Zealand strains of mice. 16 Although the cause of glucose intolerance in 10-wk-old NZB mice is still unknown, the presence of circulating ICSAs may be responsible for glucose intolerance in NZB mice at -30 wk, because the elevation of plasma glucose levels was higher in female mice, especially in mice with ICSA(++), than in male mice that showed relatively low ICSA titer.…”

“…4 However, autoantibodies to islet cells have not yet been demonstrated in NZB, NZW, or NZB/NZWF1 mice. Mononuclear cell infiltrates have been identified in the lung, liver, kidney, salivary gland, mesentery, exocrine pancreas, and, occasionally, pancreatic islets.…”