Beyond the hormone: insulin as an autoimmune target in type 1 diabetes

Endocr Rev. 2011 Oct;32(5):623-69. doi: 10.1210/er.2011-0010. Epub 2011 Jun 23.


Insulin is not only the hormone produced by pancreatic β-cells but also a key target antigen of the autoimmune islet destruction leading to type 1 diabetes. Despite cultural biases between the fields of endocrinology and immunology, these two facets should not be regarded separately, but rather harmonized in a unifying picture of diabetes pathogenesis. There is increasing evidence suggesting that metabolic factors (β-cell dysfunction, insulin resistance) and immunological components (inflammation and β-cell-directed adaptive immune responses) may synergize toward islet destruction, with insulin standing at the crossroad of these pathways. This concept further calls for a revision of the classical dichotomy between type 1 and type 2 diabetes because metabolic and immune mechanisms may both contribute to different extents to the development of different forms of diabetes. After providing a background on the mechanisms of β-cell autoimmunity, we will explain the role of insulin and its precursors as target antigens expressed not only by β-cells but also in the thymus. Available knowledge on the autoimmune antibody and T-cell responses against insulin will be summarized. A unifying scheme will be proposed to show how different aspects of insulin biology may lead to β-cell destruction and may be therapeutically exploited. We will argue about possible reasons why insulin remains the mainstay of metabolic control in type 1 diabetes but has so far failed to prevent or halt β-cell autoimmunity as an immune modulatory reagent.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoantibodies / immunology
  • Autoantigens / immunology*
  • Autoimmunity*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Environment
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Insulin / administration & dosage
  • Insulin / chemistry
  • Insulin / immunology*
  • Insulin / physiology
  • Insulin Resistance / immunology
  • Insulin-Secreting Cells / immunology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Models, Animal
  • Molecular Sequence Data
  • Proinsulin / chemistry
  • Proinsulin / genetics
  • Proinsulin / immunology
  • Protein Precursors / chemistry
  • Protein Precursors / immunology
  • Randomized Controlled Trials as Topic
  • Rats
  • Rats, Inbred BB
  • T-Lymphocytes / immunology
  • Transcription Factors


  • Autoantibodies
  • Autoantigens
  • Insulin
  • Protein Precursors
  • Transcription Factors
  • preproinsulin
  • Proinsulin