Immunohistochemical analysis of the relationship between islet cell proliferation and the production of the enteroviral capsid protein, VP1, in the islets of patients with recent-onset type 1 diabetes

Diabetologia. 2011 Sep;54(9):2417-20. doi: 10.1007/s00125-011-2192-7. Epub 2011 May 20.


Aims/hypothesis: The enteroviral capsid protein, VP1, was recently shown to be present in some beta cells in more than 60% of patients with recent-onset type 1 diabetes but in very few age-matched controls. The rate of proliferation of islet cells was also markedly increased in the type 1 diabetic patients. As it has been suggested that enteroviruses replicate most efficiently in proliferating cells, we have investigated whether VP1 is preferentially present in proliferating beta cells in type 1 diabetes.

Methods: Combined immunoperoxidase and immunofluorescence staining was used to record the presence of enteroviral VP1, insulin and Ki67 in the islets of recent-onset type 1 diabetic patients.

Results: From a total of 1,175 islets, 359 (30.5%) contained insulin. VP1-producing endocrine cells were found in 72 islets (6.1% of total), all of which retained insulin. Ki67(+) endocrine cells were present in 52 (4.4%) islets, with 44 (84.6%) of these being insulin-positive. Overall, 28 of 1,175 (2.4%) islets contained both Ki67(+) cells and VP1(+) cells. Dual positivity of these markers accounted for 38.9% of the total VP1(+) islets and 53.8% of the total Ki67(+) islets. No individual islet cells were dual-positive for Ki67 and VP1.

Conclusions/interpretation: Ki67(+) cells were frequently observed in islets that also contained VP1(+) cells, suggesting that the factors facilitating viral replication may also drive islet cell proliferation. However, in an individual cell, VP1 production does not require concurrent beta cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Capsid Proteins / metabolism*
  • Cell Proliferation*
  • Child
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / pathology
  • Enterovirus / isolation & purification
  • Enterovirus / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Infant
  • Insulin / metabolism
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / virology
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology*
  • Islets of Langerhans / virology
  • Ki-67 Antigen / metabolism
  • Male
  • Retrospective Studies
  • Virus Replication
  • Young Adult


  • Capsid Proteins
  • Insulin
  • Ki-67 Antigen