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- Title
Young NOD Mice Show Increased Diabetes Sensitivity to Low Doses of Streptozotocin.
- Authors
REDDY, SHIVA; CHANG, MIKE; ROBINSON, ELIZABETH
- Abstract
In type 1 diabetes, environmentally induced early-limited beta cell damage may pre-empt the subsequent immune-mediated beta cell destruction. Low doses of streptozotocin (Stz), given early to diabetes-prone mice, may cause limited beta cell destruction during the early phase and precipitate diabetes. Here, we aimed to see if young NOD mice are more diabetes-sensitive to various multiple low doses of Stz than nondiabetes-prone mice. We also determined the molecular pathology of islets following administration of the diabetogen. Female NOD and CD-1 mice received 5 daily doses of Stz at day 21 (20, 30, and 40 mg/kg body weight; 18 mice per group) or diluent, and diabetes was monitored. Pancreas were studied histochemically and immunohistochemically at various time points after Stz administration. Following administration of Stz, NOD mice showed a much earlier onset and increased diabetes rate, at all three doses, than CD-1 mice. By day 80, the final diabetes rates following the 40, 30, and 20 mg dose in NOD mice were 95%, 85%, and 33%, respectively, compared with 33%, 28%, and 5.5%, respectively, in CD-1 mice. However, following the 20 mg dose, only 2 of the 12 remaining NOD mice developed the disease between 90 and 250 days compared with 19 of 24 NOD mice that did not receive Stz at day 21. Stz-administered NOD and CD-1 mice showed an initial loss of beta cells, with redistribution of islet endocrine cells, early macrophage infiltration, and increasing insulitis.
- Subjects
STREPTOZOTOCIN; LABORATORY mice; DIABETES; PANCREATIC beta cells; IMMUNOHISTOCHEMISTRY; MACROPHAGES; INSULIN
- Publication
Annals of the New York Academy of Sciences, 2006, Vol 1079, Issue 1, p109
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1196/annals.1375.015