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Nonobese diabetic mice express aspects of both type 1 and type 2 diabetes

Rodolfo José Chaparro1, Yves Konigshofer, Georg F Beilhack

  • 1Program in Immunology, Division of Bone Marrow Transplantation, Stanford University Medical Center, Stanford, CA 94305, USA. rchaparr@aecom.yu.edu

Proceedings of the National Academy of Sciences of the United States of America
|August 10, 2006
PubMed

Insights

The nonobese diabetic mouse shows early abnormalities, suggesting a genetic predisposition to diabetic complications like insulin resistance, even without autoimmune destruction. This highlights a potential link between type 1 and type 2 diabetes.

Area of Science:

  • Immunology
  • Endocrinology
  • Genetics

Background:

  • Type 1 diabetes involves autoimmune destruction of pancreatic beta cells.
  • Nonobese diabetic (NOD) mice and patients exhibit pre-destruction organ abnormalities.
  • Studying these abnormalities without immune cells is crucial for understanding early disease events.

Purpose of the Study:

  • To investigate gene expression in target tissues of NOD/severe combined immunodeficient (scid) mice and resistant C57BL/6/scid mice.
  • To identify genetic factors contributing to diabetic complications independent of autoimmune destruction.
  • To explore the potential interface between type 1 and type 2 diabetes.

Main Methods:

  • Gene expression analysis in autoimmune target tissues.
  • Comparison between NOD/scid and C57BL/6/scid mice.
  • Analysis of genetic loci associated with diabetes.

Main Results:

  • NOD mice exhibit morphological and functional abnormalities in target organs.
  • These abnormalities suggest a genetic predisposition to diabetic complications, including insulin resistance.
  • Insulin resistance occurs without high glucose or autoimmune beta cell destruction.
  • Identified genes are located within known type 1 and type 2 diabetes loci.

Conclusions:

  • The NOD mouse model reveals genetic predispositions to diabetic complications independent of autoimmunity.
  • These findings suggest an overlap between type 1 and type 2 diabetes pathogenesis.
  • NOD mice are valuable for studying the early stages and potential interplay of different diabetes types.

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