Skip to main content
Top
Published in: Diabetologia 9/2011

01-09-2011 | Short Communication

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

Authors: A. Willcox, S. J. Richardson, A. J. Bone, A. K. Foulis, N. G. Morgan

Published in: Diabetologia | Issue 9/2011

Login to get access

Abstract

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.
Literature
1.
go back to reference Hober D, Sauter P (2010) Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host. Nat Rev Endocrinol 6:279–289PubMedCrossRef Hober D, Sauter P (2010) Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host. Nat Rev Endocrinol 6:279–289PubMedCrossRef
2.
go back to reference Tauriainen S, Oikarinen S, Oikarinen M, Hyöty H (2011) Enteroviruses in the pathogenesis of type 1 diabetes. Semin Immunopathol 33:45–55PubMedCrossRef Tauriainen S, Oikarinen S, Oikarinen M, Hyöty H (2011) Enteroviruses in the pathogenesis of type 1 diabetes. Semin Immunopathol 33:45–55PubMedCrossRef
3.
go back to reference Richardson SJ, Willcox A, Bone AJ, Morgan NG, Foulis AK (2011) Immunopathology of the human pancreas in type-I diabetes. Semin Immunopathol 33:9–21PubMedCrossRef Richardson SJ, Willcox A, Bone AJ, Morgan NG, Foulis AK (2011) Immunopathology of the human pancreas in type-I diabetes. Semin Immunopathol 33:9–21PubMedCrossRef
4.
go back to reference Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG (2009) The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia 52:1143–1151PubMedCrossRef Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG (2009) The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia 52:1143–1151PubMedCrossRef
5.
go back to reference Feuer R, Mena I, Pagarigan R, Slifka MK, Whitton JL (2002) Cell cycle status affects coxsackievirus replication, persistence, and reactivation in vitro. J Virol 76:4430–4440PubMedCrossRef Feuer R, Mena I, Pagarigan R, Slifka MK, Whitton JL (2002) Cell cycle status affects coxsackievirus replication, persistence, and reactivation in vitro. J Virol 76:4430–4440PubMedCrossRef
6.
go back to reference Meier JJ, Butler AE, Saisho Y et al (2008) Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans. Diabetes 57:1584–1594PubMedCrossRef Meier JJ, Butler AE, Saisho Y et al (2008) Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans. Diabetes 57:1584–1594PubMedCrossRef
7.
go back to reference Cnop M, Hughes SJ, Igoillo-Esteve M et al (2009) The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation. Diabetologia 53:321–330PubMedCrossRef Cnop M, Hughes SJ, Igoillo-Esteve M et al (2009) The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation. Diabetologia 53:321–330PubMedCrossRef
8.
go back to reference Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG (2010) Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes. Diabetologia 53:2020–2028PubMedCrossRef Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG (2010) Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes. Diabetologia 53:2020–2028PubMedCrossRef
9.
go back to reference Moya-Suri V, Schlosser M, Zimmermann K, Rjasanowski I, Gurtler L, Mentel R (2005) Enterovirus RNA sequences in sera of schoolchildren in the general population and their association with type 1-diabetes-associated autoantibodies. J Med Microbiol 54:879–883PubMedCrossRef Moya-Suri V, Schlosser M, Zimmermann K, Rjasanowski I, Gurtler L, Mentel R (2005) Enterovirus RNA sequences in sera of schoolchildren in the general population and their association with type 1-diabetes-associated autoantibodies. J Med Microbiol 54:879–883PubMedCrossRef
10.
go back to reference Stene LC, Oikarinen S, Hyoty H et al (2010) Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes 59:3174–3180PubMedCrossRef Stene LC, Oikarinen S, Hyoty H et al (2010) Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes 59:3174–3180PubMedCrossRef
11.
go back to reference Feuer R, Ruller CM, An N et al (2009) Viral persistence and chronic immunopathology in the adult central nervous system following Coxsackievirus infection during the neonatal period. J Virol 83:9356–9369PubMedCrossRef Feuer R, Ruller CM, An N et al (2009) Viral persistence and chronic immunopathology in the adult central nervous system following Coxsackievirus infection during the neonatal period. J Virol 83:9356–9369PubMedCrossRef
12.
go back to reference Feuer R, Whitton JL (2008) Preferential coxsackievirus replication in proliferating/activated cells: implications for virus tropism, persistence, and pathogenesis. Curr Top Microbiol Immunol 323:149–173PubMedCrossRef Feuer R, Whitton JL (2008) Preferential coxsackievirus replication in proliferating/activated cells: implications for virus tropism, persistence, and pathogenesis. Curr Top Microbiol Immunol 323:149–173PubMedCrossRef
13.
go back to reference Meier JJ, Lin JC, Butler AE, Galasso R, Martinez DS, Butler PC (2006) Direct evidence of attempted beta cell regeneration in an 89-year-old patient with recent-onset type 1 diabetes. Diabetologia 49:1838–1844PubMedCrossRef Meier JJ, Lin JC, Butler AE, Galasso R, Martinez DS, Butler PC (2006) Direct evidence of attempted beta cell regeneration in an 89-year-old patient with recent-onset type 1 diabetes. Diabetologia 49:1838–1844PubMedCrossRef
14.
go back to reference Maedler K, Schumann DM, Sauter N et al (2006) Low concentration of interleukin-1beta induces FLICE-inhibitory protein-mediated beta-cell proliferation in human pancreatic islets. Diabetes 55:2713–2722PubMedCrossRef Maedler K, Schumann DM, Sauter N et al (2006) Low concentration of interleukin-1beta induces FLICE-inhibitory protein-mediated beta-cell proliferation in human pancreatic islets. Diabetes 55:2713–2722PubMedCrossRef
Metadata
Title
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
Authors
A. Willcox
S. J. Richardson
A. J. Bone
A. K. Foulis
N. G. Morgan
Publication date
01-09-2011
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 9/2011
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-011-2192-7

Other articles of this Issue 9/2011

Diabetologia 9/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.