The Non-Obese Diabetic (NOD) Mouse as a Model of Human Type 1 Diabetes

Division of Immunology, Allergy, and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Methods in molecular biology (Clifton, N.J.) (Impact Factor: 1.29). 08/2012; 933:3-16. DOI: 10.1007/978-1-62703-068-7_1
Source: PubMed


The non-obese diabetic (NOD) mouse spontaneously develops type 1 diabetes (T1D) and has thus served as a model for understanding the genetic and immunological basis, and treatment, of T1D. Since its initial description in 1980, however, the field has matured and recognized that prevention of diabetes in NOD mice (i.e., preventing the disease from occurring by an intervention prior to frank diabetes) is relatively easy to achieve and does not correlate well with curing the disease (after the onset of frank hyperglycemia). Hundreds of papers have described the prevention of diabetes in NOD mice but only a handful have described its actual reversal. The paradoxical conclusion is that preventing the disease in NOD mice does not necessarily tell us what caused the disease nor how to reverse it. The NOD mouse model is therefore best used now, with respect to human disease, as a way to understand the genetic and immunologic causes of and as a model for trying to reverse disease once hyperglycemia occurs. We describe how genetic approaches to identifying causative gene variants can be adapted to identify novel therapeutic agents for reversing new-onset T1D.

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    • "Also, the antihyperglycemic activity of this protein was established by inducing diabetes in animals, and not in non-obese diabetic (NOD) mice, the spontaneous model of type 1 diabetes. The NOD mice represent one of the primary experimental models of T1DM for screening of therapeutics as these mice share many immunological and pathophysiological similarities to human insulin-dependent diabetes mellitus [13]. The present study reports comparative sequence analysis, prediction of secondary structural components, 3-dimensional structural model using in silico homology modeling and antihyperglycemic activity of the rADMc1 in non-obese diabetic (NOD) mice. "
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    ABSTRACT: Momordica charantia is a well known medicinal plant used in the traditional medicinal system for the treatment of various diseases including diabetes mellitus. Recently, a novel protein termed as ADMc1 from the seed extract of M. charantia has been identified and isolated showing significant antihyperglycemic activity in type 1 diabetic rats in which diabetes was induced. However, the structure of this protein has not yet been analyzed. Homology modeling approach was used to generate a high quality protein 3D structure for the amino acid sequence of the ADMc1 protein in this study. The comparative assessment of secondary structures revealed ADMc1 as an all-alpha helix protein with random coils. Tertiary structure predicted on the template structure of Napin of B. Napus (PDB ID: 1SM7) with which the ADMc1 showed significant sequence similarity, was validated using protein structure validation tools like PROCHECK, WHAT_CHECK, VERIFY3D and ProSA. Arrangement of disulfide bridges formed by cysteine residues were predicted by the Dianna 1.1 server. The presence of multiple disulfide bond confers the stable nature of the ADMc1 protein. Further, the biological activity of the ADMc1 was assessed in non-obese diabetic (NOD) mice which are spontaneous model of type 1 diabetes. Significant reduction in the blood glucose levels of NOD mice was observed up to 8 h post administration of the rADMc1 protein. Overall, the structural characterizations with antihyperglycemic activity of this seed protein of Momordica charantia demonstrate its potential as an antidiabetic agent.
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    ABSTRACT: The development of therapies that specifically target autoreactive immune cells for the prevention and treatment of type 1 diabetes (T1D) without inducing generalized immunosuppression that often compromises the host's ability to clear non-self antigen is highly desired. This review discusses the mechanisms and potential therapeutic applications of antigen-specific T cell tolerance techniques using syngeneic apoptotic cellular carriers and synthetic nanoparticles that are covalently cross-linked to diabetogenic peptides or proteins through ethylene carbodiimide (ECDI) to prevent and treat T1D. Experimental models have demonstrated that intravenous injection of autoantigen decorated splenocytes and biodegradable nanoparticles through ECDI fixation effectively induce and maintain antigen-specific T cell abortive activation and anergy by T cell intrinsic and extrinsic mechanisms. The putative mechanisms include, but are not limited to, the uptake and processing of antigen-coupled nanoparticles or apoptotic cellular carriers for tolerogenic presentation by host splenic antigen-presenting cells, the induction of regulatory T cells, and the secretion of immune-suppressive cytokines, such as IL-10 and TGF-β. The safety profile and efficacy of this approach in preclinical animal models of T1D, including non-obese diabetic (NOD), BDC2.5 transgenic, and humanized mice, have been extensively investigated, and will be the focus of this review. Translation of this approach to clinical trials of T1D and other T cell-mediated autoimmune diseases will also be reviewed in this chapter.
    Preview · Article · Jan 2012 · The Review of Diabetic Studies
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    ABSTRACT: Aim: The aim of this study was to evaluate the relationship between pulpal and/or periodontal disease and serum creatinine levels in a rat model of diabetes mellitus. Methods: Eighty male rats (Rattus norvegicus albinus, Wistar) were divided into the following 8 groups compris- ing 10 animals each: normal (G1), with pulpal disease (G2), with periodontal disease (G3), with both pulpal and periodontal disease (G4), diabetic (G5), diabetic with pulpal disease (G6), diabetic with periodontal disease (G7), and diabetic with both pulpal and periodontal disease (G8). Diabetes was induced by injecting streptozotocin, pul- pal disease were induced by exposing pulpal tissue to the oral environment, and periodontal disease was induced by periodontal ligature. After 30 days, blood was collected by cardiac puncture and the animals were killed. The maxillae were processed for histopathology. Serum creatinine levels were measured by the enzymatic method. The total assessed values were statistically analyzed by analysis of variance and Tukey’s test (p < 0.05). Results:􏰢􏰣􏰥􏰲􏰤􏰯􏰢􏰳􏰲􏰥􏰬􏰴􏰪􏰫􏰪􏰫􏰥􏰢􏰦􏰥􏰵􏰥􏰦􏰶􏰢􏰷􏰥􏰲􏰥􏰢􏰶􏰪􏰩􏰫􏰪􏰱􏰳􏰬􏰫􏰴􏰦􏰧􏰢􏰸􏰪􏰩􏰸􏰥􏰲􏰢􏰪􏰫􏰢􏰹􏰪􏰬􏰺􏰥􏰴􏰪􏰳􏰢􏰲􏰬􏰴􏰶􏰢􏰴􏰸􏰬􏰫􏰢􏰴􏰸􏰬􏰴􏰢􏰪􏰫􏰢􏰬􏰦􏰦􏰢􏰫􏰮􏰲􏰯􏰮􏰩􏰦􏰧􏰳􏰥􏰯􏰪􏰳􏰢􏰲􏰬􏰴􏰶􏰢􏰻􏰼􏰢􏰽􏰢 0.05). The presence of pulpal and periodontal disease increased the serum creatinine levels in normoglycemic and diabetic rats, but there was no statistical difference between the groups (p > 0.05). Conclusions: We found that the serum creatinine level was higher in diabetic rats and may be related to the pres- ence of oral infections. 􏰾􏰦􏰪􏰫􏰪􏰳􏰬􏰦􏰢􏰶􏰪􏰩􏰫􏰪􏰱􏰳􏰬􏰫􏰳􏰥􏰿􏰢Changes in serum creatinine level may be related to the presence of oral infections and diabetes. Keywords: Diabetes; Apical Periodontitis; Periodontal Disease; Creatinine Level
    No preview · Article · Jan 2013
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