Type 1 Diabetes – cause and cure

This project applies clinically-reflective model systems and human tissue studies to determine the disease mechanisms underpinning the causes, development and progression of diabetes.

Early work documenting the natural history of the disease processes in models of Type 1 Diabetes (T1D) has progressed to studies on newly diagnosed diabetes in humans.

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Project timeframes

This project began in 2007 and is ongoing.

Project aims

Ongoing collaborative research projects are aimed at:

  • detecting the persistent enterovirus infection leading to inflammation and damage of the pancreas and stopping the subsequent development of T1D;
  • understanding the beta-cell defence and repair mechanisms during the onset and progression of diabetes.

 

Project findings and impact

Project findings using a unique collection of T1D pancreases, have characterised the inflammatory infiltrate in T1D and provided the first direct evidence that a common enteroviral infection is capable of triggering development of diabetes in genetically susceptible individuals. This work was identified as a ‘Research Highlight’ in Nature. Further research demonstrated for the first time that there is an increased islet cell proliferation in patients with recent-onset T1D thereby identifying new therapeutic targets and treatments for the cure and prevention of T1D (Juvenile Diabetes Research Federation International–Research Priority Area).

Taken together, these new studies have opened up the exciting possibility of:

  • producing a vaccine that could ultimately significantly reduce the number of children who develop diabetes and
  • developing therapies which could allow patients with T1D to sustain or renew their own capacity to produce insulin.

Research team

Professor Adrian Bone

Dr Wendy M Macfarlane

Dr Claire E Marriott

James Bockhart

Sandeep Kumar

Nouf Alhasawi

Output

Current Project Funding:

2011 – 2016. EU Seventh FP Collaborative Project: 5.99 million Euros awarded – “PEVNET” Persistent virus infection as a cause of pathogenic inflammation in type 1 diabetes – an innovative research programme of biobanks and expertise (AJB together with Prof N.G. Morgan, Prof A.K. Foulis & 13 EU Partners)

Selected Publications:

Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG. The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia 2009; 52: 1143-1151

Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol 2009: 155: 173-181

Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG. Islet associated macrophages in type 2 diabetes. Diabetologia 2009; 52: 1686-1688

Richardson SJ, Willcox A, Hilton DA, Tauriainen S, Hyoty H, Bone AJ, Foulis AK, Morgan NG. Use of antisera directed against dsRNA to detect viral infections in formalin-fixed, paraffin-embedded tissues. J. Clin Virol 2010: 49: 180-185

Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. Evidence of increased islet cell proliferation in patients with recent onset type 1 diabetes. Diabetologia 2010: Editors Choice; 53: 2020 - 2028

Richardson SJ, Willcox A, Bone AJ, Morgan NG, Foulis AK. Immunopathology of the human pancreas in type 1 diabetes. Semin Immunopathol 2011: 33: 9-21

Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. 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: Short Communication; 54: 2417 – 2420 * see Comment article below.

*In’t Veld P. Insulitis in the human endocrine pancreas: does viral infection lead to inflammation and beta cell replication. Diabetologia 2011: Comment; 54: 2220 – 2222

Richardson SJ, Willcox A, Bone AJ, Morgan NG, Foulis AK. Viruses in the human pancreas. In: Diabetes and Viruses. A Toniolo (Ed) 2012: Springer Science New York. DOI 10.1007/978-1-4614-4051-2 - 17

Richardson SJ, Leete P, Bone AJ, Foulis AK, Morgan NG. Expression of the enteroviral capsid protein, VP1, in the islet cells of patients with type 1 diabetes is associated with induction of protein kinase R and down-regulation of Mcl-1. Diabetologia 2013: 56: 185 – 193

Richardson SJ, Leete P, Dhayal S, Russell MA, Oikarinen M, Laiho JE, Svedin E, Lind K, Roseling T, Chapman N, Bone AJ, The nPOD-V consortium, Foulis AK, Frisk G, Flodstrom-Tullberg M, Hober D, Hyoty H, Morgan NG. Evaluation of the fidelity of immunolabelling obtained with clone 5DA/1, a monoclonal antibody directed against the enteroviral capsid protein, VP1, in human pancreas. Diabetologia 2013;  56(1): 185-93.

Richardson SJ, Leete P, Dhayal S, Russell MA, Oikarinen M, Laiho JE, Svedin E, Lind K, Rosenling T, Chapman N, Bone AJ, nPOD-V Consortium, Foulis AK, Frisk G, Flodstrom-Tullberg M, Hober D, Hyoty H, Pugliese A, Morgan NG. Evaluation of the fidelity of immunolabelling obtained with clone 5D8/1, a monoclonal antibody directed against the enteroviral capsid protein, VP1, in human pancreas. Diabetologia 2014; 57 (2):392-401.        

Richardson SJ, Leete P, Dhayal S, Russell MA, Oikarinen M, Laiho JE, Svedin E, Lind K, Rosenling T, Chapman N, Bone AJ, Foulis AK, Frisk G, Flodstrom-Tullberg M, Hober D, Hyoty H, Pugliese A, Morgan NG. Detection of enterovirus in the wilst cells of patients with type I diabetes: what do we learn from immunohistochemistry [Letter]. Diabetologia 2014 Jan 16. [Epub ahead of print].

Partners

Diabetes Research Group projects continue to be enhanced and expanded through strategic national (Exeter, Newcastle, Bristol, Glasgow, Plymouth, Sussex) and international (USA, South Africa, Sweden, Ireland, Germany) academic scientific collaboration, as well as strategic links with local academic and healthcare organisations.