Hindawi Publishing Corporation Journal of Diabetes Research Volume 2013, Article ID 965832, 13 pages http://dx.doi.org/10.1155/2013/965832 Research Article Variations in Rodent Models of Type 1 Diabetes: Islet Morphology Lesya Novikova, 1 Irina V. Smirnova, 1 Sonia Rawal, 1 Abby L. Dotson, 2 Stephen H. Benedict, 2 and Lisa Stehno-Bittel 1 1 Department of Physical herapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, KS 66160, USA 2 Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA Correspondence should be addressed to Lisa Stehno-Bittel; lbittel@kumc.edu Received 6 February 2013; Accepted 18 April 2013 Academic Editor: Norman Cameron Copyright © 2013 Lesya Novikova et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Type 1 diabetes (T1D) is characterized by hyperglycemia due to lost or damaged islet insulin-producing -cells. Rodent models of T1D result in hyperglycemia, but with diferent forms of islet deterioration. his study focused on 1 toxin-induced and 2 autoimmune rodent models of T1D: BioBreeding Diabetes Resistant rats, nonobese diabetic mice, and Dark Agouti rats treated with streptozotocin. Immunochemistry was used to evaluate the insulin levels in the -cells, cell composition, and insulitis. T1D caused complete or signiicant loss of -cells in all animal models, while increasing numbers of -cells. Lymphocytic iniltration was noted in and around islets early in the progression of autoimmune diabetes. he loss of lymphocytic iniltration coincided with the absence of -cells. In all models, the remaining - and -cells regrouped by relocating to the islet center. he resulting islets were smaller in size and irregularly shaped. Insulin injections subsequent to induction of toxin-induced diabetes signiicantly preserved -cells and islet morphology. Diabetes in animal models is anatomically heterogeneous and involves important changes in numbers and location of the remaining - and -cells. Comparisons with human pancreatic sections from healthy and diabetic donors showed similar morphological changes to the diabetic BBDR rat model. 1. Introduction Rodent models of diabetes are frequently used in basic sci- ence and in industrial environments, such as the pharma- ceutical industry. Animal models of diabetes have been used for the past 150 years and were instrumental in the discovery of insulin [1]. In humans with type 1 diabetes (T1D), it is estimated that 70% of the pancreatic -cell mass has been destroyed by the time clinical signs of the disease are present [2]. Without safe methods of sampling or visualizing the human endocrine pancreas, animals are essential models of the disease. Rodent models have enabled the discovery of key scientiic indings, but frequently these indings do not translate to the clinical setting [2]. he common rodent models of T1D include the Bio- Breeding Diabetes-Resistant (BBDR) rat, the nonobese dia- betic (NOD) mice, and the streptozotocin-induced diabetic rodents. Rodents studied for T1D can be broadly classiied as having either spontaneous or inducible forms of the disease. In spontaneous diabetes, such as the NOD mouse, the genetic background results in a deined prevalence of the disease [2]. In contrast, with inducible diabetes, the disease is precipitated by exposure to deined antigens or reagents [2]. While the endpoint of hyperglycemia is the same, the path to eventual diabetes is quite diferent in each case. he NOD mouse is an inbred strain that spontaneously develops autoimmune diabetes similar in pattern and genetic susceptibility loci to human T1D [1, 3]. Although it has been around for over 30 years, it still remains a pillar of diabetes research [4] with over 8000 publications utilizing the model. Interestingly, NOD mice housed in pathogen-free facilities exhibit an increased incidence of diabetes relative to those housed in conventional facilities [3]. he original BioBreeding rat colony was established in Canada in the 1970s. Fity percent of the rats from the original line developed diabetes spontaneously. Since human clinical data suggested that diabetes was associated with environmen- tal factors such as viral exposures [5–7], a virally inducible