On the etiology of type 1 diabetes: a new animal model signifying a decisive role for bacteria eliciting an adverse innate immunity response

Am J Pathol. 2012 Nov;181(5):1735-48. doi: 10.1016/j.ajpath.2012.07.022. Epub 2012 Sep 1.


The cause of type 1 diabetes (T1D) remains unknown; however, a decisive role for environmental factors is recognized. The increased incidence of T1D during the last decades, as well as regional differences, is paralleled by differences in the intestinal bacterial flora. A new animal model was established to test the hypothesis that bacteria entering the pancreatic ductal system could trigger β-cell destruction and to provide new insights to the immunopathology of the disease. Obtained findings were compared with those present in two patients dying at onset of T1D. Different bacterial species, present in the human duodenum, instilled into the ductal system of the pancreas in healthy rats rapidly induced cellular infiltration, consisting of mainly neutrophil polymorphonuclear cells and monocytes/macrophages, centered around the pancreatic ducts. Also, the islets of Langerhans attracted polymorphonuclear cells, possibly via release of IL-6, IL-8, and monocyte chemotactic protein 1. Small bleedings or large dilatations of the capillaries were frequently found within the islets, and several β-cells had severe hydropic degeneration (ie, swollen cytoplasm) but with preserved nuclei. A novel rat model for the initial events in T1D is presented, revealing marked similarities with the morphologic findings obtained in patients dying at onset of T1D and signifying a decisive role for bacteria in eliciting an adverse innate immunity response. The present findings support the hypothesis that T1D is an organ-specific inflammatory disease.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Bacteria / immunology*
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / microbiology*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / physiopathology
  • Disease Models, Animal
  • Fatal Outcome
  • Humans
  • Immunity, Innate / immunology*
  • Immunohistochemistry
  • Inflammation / complications
  • Inflammation / immunology
  • Inflammation / pathology
  • Islets of Langerhans / immunology
  • Islets of Langerhans / microbiology
  • Islets of Langerhans / pathology
  • Islets of Langerhans / physiopathology
  • Male
  • Models, Biological
  • Rats
  • Rats, Wistar


  • Cytokines