Abstract
During type 1 diabetes, most beta cells die by immune processes. However, the precise fate and characteristics of beta cells and islet autoimmunity after onset are unclear. Here, the extent of beta cell survival was determined in the non-obese diabetic (NOD) mouse during increasing duration of disease and correlated with insulitis. Pancreata from female NOD mice at diagnosis and at 1, 2, 3 and 4 weeks thereafter were analysed immunohistochemically for insulin, glucagon and somatostatin cells and glucose transporter-2 (glut2) and correlated with the degree of insulitis and islet immune cell phenotypes. Insulitis, although variable, persisted after diabetes and declined with increasing duration of disease. During this period, beta cells also declined sharply whereas glucagon and somatostatin cells increased, with occasional islet cells co-expressing insulin and glucagon. Glut2 was absent in insulin-containing cells from 1 week onwards. CD4 and CD8 T cells and macrophages persisted until 4 weeks, in islets with residual beta cells or extensive insulitis. We conclude that after diabetes onset, some beta cells survive for extended periods, with continuing autoimmunity and expansion of glucagon and somatostatin cells. The absence of glut2 in several insulin-positive cells suggests that some beta cells may be unresponsive to glucose.
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Acknowledgements
We thank Beryl Davy and Lorraine Rolston for expert histological support and Jacqueline Ross for valuable advice on image preparation and Vernon Tintinger for assistance with the careful maintenance of the NOD mouse colony. Financial assistance from the Child Health Research Foundation, the Maurice & Phyllis Paykel Trust, University of Auckland School of Biological Sciences Summer Studentship Programme and the Auckland Medical Research Foundation is gratefully acknowledged.
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Reddy, S., Chai, R., Rodrigues, J.A. et al. Presence of residual beta cells and co-existing islet autoimmunity in the NOD mouse during longstanding diabetes: a combined histochemical and immunohistochemical study. J Mol Hist 39, 25–36 (2008). https://doi.org/10.1007/s10735-007-9122-5
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DOI: https://doi.org/10.1007/s10735-007-9122-5