Pancreatic pathology in type 1 diabetes in human

Novartis Found Symp. 2008;292:2-13; discussion 13-8, 122-9, 202-3.

Abstract

In type 1 autoimmune diabetes there is a selective destruction of insulin-secreting beta cells. Around the time of clinical presentation, insulitis, a chronic inflammatory infiltrate of the islets affecting primarily insulin containing islets, is present in the majority of cases. The inflammatory infiltrate consists primarily of T lymphocytes; CD8 cells outnumber CD4 cells, there are fewer B lymphocytes and macrophages are relatively scarce. beta cell death may involve the Fas apoptotic pathway since they have been shown to express Fas, infiltrating T lymphocytes express Fas-L and apoptotic beta cells have been described. Hyperexpression of class I MHC by all the endocrine cells in many insulin-containing islets is a well recognized phenomenon, characteristic of the disease. It has been argued that this is an earlier event than insulitis within a given islet and appears to be due to secretion of interferon alpha by beta cells within that islet. A recent study has found evidence of Coxsackie virus infection in beta cells in three out of six pancreases of patients with recent-onset type 1 diabetes. Coxsackie viruses are known to induce interferon alpha secretion by beta cells and this could initiate the sequence of events that culminates in their autoimmune destruction.

MeSH terms

  • Apoptosis / immunology
  • Coxsackievirus Infections / complications
  • Coxsackievirus Infections / immunology
  • Coxsackievirus Infections / pathology*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetes Mellitus, Type 1 / virology*
  • Fas Ligand Protein / immunology
  • Fas Ligand Protein / metabolism
  • Histocompatibility Antigens / immunology
  • Histocompatibility Antigens / metabolism
  • Humans
  • Inflammation / pathology
  • Insulin / immunology
  • Insulin / metabolism
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / pathology*
  • Insulin-Secreting Cells / virology*
  • Pancreas / immunology
  • Pancreas / pathology
  • Pancreas / virology
  • fas Receptor / immunology
  • fas Receptor / metabolism

Substances

  • Cytokines
  • Fas Ligand Protein
  • Histocompatibility Antigens
  • Insulin
  • fas Receptor