Role of β-Cells in Type 1 Diabetes Pathogenesis

  1. Béatrice Faideau,
  2. Etienne Larger,
  3. Françoise Lepault,
  4. Jean Claude Carel and
  5. Christian Boitard
  1. From the INSERM U561, Hôpital Cochin-Saint Vincent de Paul, Paris, France
  1. Address correspondence and reprint requests to Christian Boitard, INSERM U561, Hôpital St. Vincent de Paul, 82 Avenue Denfert Rochereau, 75014 Paris, France. E-mail: boitard{at}paris5.inserm.fr

Abstract

Whether autoimmunity results primarily from a defect of the immune system, target organ dysfunction, or both remains an open issue in most human autoimmune diseases. The highly multigenic background on which diabetes develops in the NOD mouse and in the human suggests that numerous gene variants associate in contributing to activation of autoimmunity to β-cells. Both immune genes and islet-related genes are involved. The presence of β-cells is required for initiation of diabetes autoimmunity to proceed. Available experiments in the NOD mouse and epidemiological evidence in the human point to proinsulin as a key autoantigen in diabetes. The functional importance of insulin, the high number of autoantigens characterized at different stages of diabetes, and their clustering within β-cell subparticles point to the islet as a starting point in the initiation phase of the disease. Genes that direct the autoimmune reaction toward the β-cell target, autoantigens that are recognized by autoreactive B- and T-cells along the autoimmune process, the importance of β-cells in the activation of autoreactive lymphocytes, and the expression level of key β-cell molecules along diabetes development are successively considered in this review.

Footnotes

  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.

    • Accepted May 23, 2005.
    • Received March 11, 2005.
| Table of Contents