Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?

Diabetes. 2017 Jun;66(6):1443-1452. doi: 10.2337/db16-1551.


Despite decades of research in humans and mouse models of disease, substantial gaps remain in our understanding of pathogenic mechanisms underlying the development of type 1 diabetes. Furthermore, translation of therapies from preclinical efforts capable of delaying or halting β-cell destruction has been limited. Hence, a pressing need exists to identify alternative animal models that reflect human disease. Canine insulin deficiency diabetes is, in some cases, considered to follow autoimmune pathogenesis, similar to NOD mice and humans, characterized by hyperglycemia requiring lifelong exogenous insulin therapy. Also similar to human type 1 diabetes, the canonical canine disorder appears to be increasing in prevalence. Whereas islet architecture in rodents is distinctly different from humans, canine pancreatic endocrine cell distribution is more similar. Differences in breed susceptibility alongside associations with MHC and other canine immune response genes parallel that of different ethnic groups within the human population, a potential benefit over NOD mice. The impact of environment on disease development also favors canine over rodent models. Herein, we consider the potential for canine diabetes to provide valuable insights for human type 1 diabetes in terms of pancreatic histopathology, impairment of β-cell function and mass, islet inflammation (i.e., insulitis), and autoantibodies specific for β-cell antigens.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Autoantibodies / immunology*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / pathology
  • Disease Models, Animal*
  • Dogs*
  • HLA Antigens / genetics
  • Histocompatibility Antigens / genetics
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Inflammation
  • Insulin / metabolism
  • Insulin / therapeutic use
  • Insulin Secretion
  • Insulin-Secreting Cells / immunology*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology
  • Mice
  • Mice, Inbred NOD
  • Pancreas / pathology
  • Rats


  • Autoantibodies
  • HLA Antigens
  • Histocompatibility Antigens
  • Hypoglycemic Agents
  • Insulin