dc.contributor.advisor |
Reddy, S |
en |
dc.contributor.author |
Martin, Charlton |
en |
dc.date.accessioned |
2016-05-24T21:42:02Z |
en |
dc.date.issued |
2015 |
en |
dc.identifier.citation |
2015 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/28900 |
en |
dc.description |
Full text is available to authenticated members of The University of Auckland only. |
en |
dc.description.abstract |
Type 1 diabetes (T1D) results from a complex but poorly defined interaction between genetic and environmental factors during which autoimmune-mediated beta cell destruction occurs. Beta cells are poorly equipped in clearing excess oxidants causing cellular stress through accumulation of reactive oxygen and nitrogen species. These can damage beta cells through peroxynitrite-mediated beta cell nitration. The aim of the present research was to seek evidence of beta cell nitration within cadaveric pancreas of humans as a function of different duration of T1D and without disease and its effect on leukocyte infiltration of the islet. A triple staining immunohistochemical procedure for detecting nitrotyrosine (a biomarker for cellular nitration), insulin and CD45 (a biomarker for leukocytes) was validated and applied to pancreatic sections, provided by the Network for Pancreatic Organ Donors with Diabetes, USA and from the Diabetes Virus Detection Study, Norway. We studied non-diabetic donors (n=7), non-diabetic, autoantibody positive donors (n=6) and patients with recent-onset T1D (n=6), 1-5 years of T1D (n=8) and 7-12 years of disease (n=6; total number of cases = 33). Each slide was triple-stained for nitrotyrosine, insulin and CD45 and images recorded. CD45 staining was used for assessment of insulitis within each islet (insulitis) and correlated with the degree and intensity of nitrotyrosine staining per case and per islet. Nitrotyrosine was localized exclusively within beta cells that were contained within the pancreatic islets. In non-diabetic cases, the median percentage of islets per section showing nitrotyrosine immunolabelling was 41.61%, whereas in recent-onset cases it was 59.44%. Leukocyte infiltration was observed to be highest in the recent-onset cases whereas only a small number of islets infiltrated by leukocytes was observed in non-diabetic cases; however, this was not observed to be related to the degree of nitrotyrosine staining. These results suggest that although non-diabetic cases suffer from a moderate level of underlying stress, beta cells undergo an increased amount of stress soon after onset of diabetes. This stress marker may act in concert with other deleterious factors in promoting beta cell destruction during T1D. Thus, examination of other stress markers using a larger cohort of cases and how beta cell stress pathways form a complex nexus with the immune system are warranted. |
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dc.publisher |
ResearchSpace@Auckland |
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dc.relation.ispartof |
Masters Thesis - University of Auckland |
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dc.relation.isreferencedby |
UoA99264849804602091 |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
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dc.rights |
Restricted Item. Available to authenticated members of The University of Auckland. |
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dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ |
en |
dc.title |
Beta cells as early initiators of autoimmune type 1 diabetes: Molecular and cellular clues by directly comparing pancreas from humans before and after clinical onset |
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dc.type |
Thesis |
en |
thesis.degree.discipline |
Biomedical Science |
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thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Masters |
en |
dc.rights.holder |
Copyright: The Author |
en |
pubs.elements-id |
528111 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Te Kupenga Hauora Maori |
en |
pubs.org-id |
Vision 2020 Service |
en |
pubs.record-created-at-source-date |
2016-05-25 |
en |
dc.identifier.wikidata |
Q112909846 |
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