Use of Nonobese Diabetic Mice to Understand Human Type 1 Diabetes

Thayer, Terri C.; Wilson, S. Brian; Mathews, Clayton E.

doi:10.1016/j.ecl.2010.05.001

Cited by 71 publications

(52 citation statements)

References 139 publications

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“…As expected, NOD mice displayed increased glucose beginning at 15 wk ( Figure 1) and is consistent with the phenotype of this autoimmune T1D mouse model [11][12][13] . The growth characteristics were then determined between NOD and NOD.scid mice.…”

Section: Resultssupporting

confidence: 54%

“…Autoimmune-prone non-obese diabetic (NOD) mice are a widely studied model of spontaneous type 1 diabetes (T1D) [11][12][13] . In contrast to the pharmacologic streptozotocin (STZ)-induced T1D model, NOD mice become spontaneously diabetic secondary to a progressive diminished capacity of insulin-producing pancreatic beta islet cell function due to autoimmune destruction of the islet beta-cells.…”

Section: Introductionmentioning

confidence: 99%

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Diabetes-related impairment in bone strength is established early in the life course

Casazza

Hanks²,

Clines³

et al. 2013

WJD

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AIM:To evaluate properties of bone quantity/quality using young non-obese Type 1 (T1D)-diabetic (NOD) prone and syngenic non-diabetic (NOD.scid ) mice. METHODS:Quantitative bone assessment of tibia was conducted using dual-energy X-ray absorptiometry (DXA) for the evaluation of body mass, bone mineral content, body fat mass and lean mass. Qualitative assessment was accomplished by three-point breakage for assessment of force to failure and micro-computed tomography for evaluation of trabecular and cortical properties of bone. In addition, fasting blood was evaluated prior to sacrifice at week eleven and fifteen to evaluate and compare glucose homeostasis between the strains of mice. RESULTS:Our findings support a perturbation in the relationship between bone quantity, quality, and subsequently, the association between structure and strength. There were no differences in DXA-assessed body composition (body fat, % fat mass and lean mass) and bone composition (bone mineral content and bone mineral density) between strains. However, relative to NOD.scid , NOD mice had lower trabecular bone volume, relative trabecular bone volume, trabecular number and trabecular total material density (P < 0.05). Conversely, NOD mice had greater cortical total mean volume (P < 0.05). General linear models analysis adjusted for body weight revealed a significant contribution of T1D to bone health as early as 5 wk. CONCLUSION:It is well-established that diabetes is a significant risk factor for increased fractures, although the underlying mechanisms are not fully understood. Investigation of bone parameters encompassing strength and structure early in the life course will facilitate the elucidation of the pathogenesis of impaired bone integrity.

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Section: Resultssupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Diabetes-related impairment in bone strength is established early in the life course

Casazza

Hanks²,

Clines³

et al. 2013

WJD

View full text Add to dashboard Cite

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“…In T1D, autoimmune recognition of beta cell antigens leads to the progressive destruction of beta cells. A similar process occurs spontaneously in the NOD mouse, leading to extensive beta cell loss and diabetes, though on a shorter time scale than in human T1D; this model, sharing many similar features with human T1D, has been used extensively to research the immunological processes underlying T1D (Thayer et al 2010). Many beta cell antigens, targeted by one or both of the humoral (autoantibodies) and cellular (autoreactive T cells) branches of adaptive immunity, have been identified in NOD mice and humans (Roep & Peakman 2012).…”

Section: Iapp As An Autoantigen In Type 1 Diabetesmentioning

confidence: 99%

IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants

Denroche

Verchere

2018

Journal of Molecular Endocrinology

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Islet amyloid polypeptide (IAPP), the main component of islet amyloid in type 2 diabetes and islet transplants, is now recognized as a contributor to beta cell dysfunction. Increasingly, evidence warrants its investigation in type 1 diabetes owing to both its immunomodulatory and metabolic actions. Autoreactive T cells to IAPP-derived epitopes have been described in humans, suggesting that IAPP is an islet autoantigen in type 1 diabetes. In addition, although aggregates of IAPP have not been implicated in type 1 diabetes, they are potent pro-inflammatory stimuli to innate immune cells, and thus, could influence autoimmunity. IAPP aggregates also occur rapidly in transplanted islets and likely contribute to islet transplant failure in type 1 diabetes through sterile inflammation. In addition, since type 1 diabetes is a disease of both insulin and IAPP deficiency, clinical trials have examined the potential benefits of IAPP replacement in type 1 diabetes with the injectable IAPP analogue, pramlintide. Pramlintide limits postprandial hyperglycemia by delaying gastric emptying and suppressing hyperglucagonemia, underlining the possible role of IAPP in postprandial glucose metabolism. Here, we review IAPP in the context of type 1 diabetes: from its potential involvement in type 1 diabetes pathogenesis, through its role in glucose metabolism and use of IAPP analogues as therapeutics, to its potential role in clinical islet transplant failure and considerations in this regard for future beta cell replacement strategies.

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“…T1D is a polygenic disease, with over 50 genetic linkages identified in both human and mouse that are associated with this autoimmune disease (recently reviewed in [2]). The identification of loci contributing to T1D has been accomplished through arranged marriages of NOD with more than 10 inbred mouse strains ( Table 2).…”

Section: Similarities In Genetic Causationmentioning

confidence: 99%

“…humans and NOD mice [2], including comparisons of the immunologic and genetic contributions (Table 1). However, emerging evidence from translational efforts forms a unique starting point for a comparison of human and NOD mouse autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

Comparative Genetics: Synergizing Human and NOD Mouse Studies for Identifying Genetic Causation of Type 1 Diabetes

Driver¹,

Chen²,

Mathews³

2012

Rev Diabet Stud

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Although once widely anticipated to unlock how human type 1 diabetes (T1D) develops, extensive study of the nonobese diabetic (NOD) mouse has failed to yield effective treatments for patients with the disease. This has led many to question the usefulness of this animal model. While criticism about the differences between NOD and human T1D is legitimate, in many cases disease in both species results from perturbations modulated by the same genes or different genes that function within the same biological pathways. Like in humans, unusual polymorphisms within an MHC class II molecule contributes the most T1D risk in NOD mice. This insight supports the validity of this model and suggests the NOD has been improperly utilized to study how to cure or prevent disease in patients. Indeed, clinical trials are far from administering T1D therapeutics to humans at the same concentration ranges and pathological states that inhibit disease in NOD mice. Until these obstacles are overcome it is premature to label the NOD mouse a poor surrogate to test agents that cure or prevent T1D. An additional criticism of the NOD mouse is the past difficulty in identifying genes underlying T1D using conventional mapping studies. However, most of the few diabetogenic alleles identified to date appear relevant to the human disorder. This suggests that rather than abandoning genetic studies in NOD mice, future efforts should focus on improving the efficiency with which diabetes susceptibility genes are detected. The current review highlights why the NOD mouse remains a relevant and valuable tool to understand the genes and their interactions that promote autoimmune diabetes and therapeutics that inhibit this disease. It also describes a new range of technologies that will likely transform how the NOD mouse is used to uncover the genetic causes of T1D for years to come.

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Use of Nonobese Diabetic Mice to Understand Human Type 1 Diabetes

Cited by 71 publications

References 139 publications

Diabetes-related impairment in bone strength is established early in the life course

Diabetes-related impairment in bone strength is established early in the life course

IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants

Comparative Genetics: Synergizing Human and NOD Mouse Studies for Identifying Genetic Causation of Type 1 Diabetes

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