Biobreeding rat islets exhibit reduced antioxidative defense and N-acetyl cysteine treatment delays type 1 diabetes
(2013) In Journal of Endocrinology 216(2). p.111-123- Abstract
- Islet-level oxidative stress has been proposed as a trigger for type 1 diabetes (T1D), and release of cytokines by infiltrating immune cells further elevates reactive oxygen species (ROS), exacerbating beta cell duress. To identify genes/mechanisms involved with diabeto-genesis at the beta cell level, gene expression profiling and targeted follow-up studies were used to investigate islet activity in the biobreeding (BB) rat. Forty-day-old spontaneously diabetic lymphopenic BB DRlyp/lyp rats (before T cell insulitis) as well as nondiabetic BB DR+/+ rats, nondiabetic but lymphopenic F344lyp/lyp rats, and healthy Fischer (F344) rats were examined. Gene expression profiles of BB rat islets were highly distinct from F344 islets and... (More)
- Islet-level oxidative stress has been proposed as a trigger for type 1 diabetes (T1D), and release of cytokines by infiltrating immune cells further elevates reactive oxygen species (ROS), exacerbating beta cell duress. To identify genes/mechanisms involved with diabeto-genesis at the beta cell level, gene expression profiling and targeted follow-up studies were used to investigate islet activity in the biobreeding (BB) rat. Forty-day-old spontaneously diabetic lymphopenic BB DRlyp/lyp rats (before T cell insulitis) as well as nondiabetic BB DR+/+ rats, nondiabetic but lymphopenic F344lyp/lyp rats, and healthy Fischer (F344) rats were examined. Gene expression profiles of BB rat islets were highly distinct from F344 islets and under-expressed numerous genes involved in ROS metabolism, including glutathione S-transferase (GST) family members (Gstm2, Gstm4, Gstm7, Gstt1, Gstp1, and Gstk1), superoxide dismutases (Sod2 and Sod3), peroxidases, and peroxiredoxins. This pattern of under-expression was not observed in brain, liver, or muscle. Compared with F344 rats, BB rat pancreata exhibited lower GST protein levels, while plasma GST activity was found significantly lower in BB rats. Systemic administration of the antioxidant N-acetyl cysteine to DRlyp/lyp rats altered abundances of peripheral eosinophils, reduced severity of insulitis, and significantly delayed but did not prevent diabetes onset. We find evidence of b cell dysfunction in BB rats independent of T1D progression, which includes lower expression of genes related to antioxidative defense mechanisms during the pre-onset period that may contribute to overall T1D susceptibility. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3671275
- author
- Bogdani, Marika
; Henschel, Angela M.
; Kansra, Sanjay
; Fuller, Jessica M.
; Geoffrey, Rhonda
; Jia, Shuang
; Kaldunski, Mary L.
; Pavletich, Scott
; Prosser, Simon
; Chen, Yi-Guang
; Lernmark, Åke
LU
and Hessner, Martin J.
(Less) - organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Endocrinology
- volume
- 216
- issue
- 2
- pages
- 111 - 123
- publisher
- Society for Endocrinology
- external identifiers
-
- wos:000315733400003
- scopus:84874778734
- pmid:23111281
- ISSN
- 1479-6805
- DOI
- 10.1530/JOE-12-0385
- language
- English
- LU publication?
- yes
- id
- ae348fa8-ae08-428d-9a7b-a5ffcb82d9ad (old id 3671275)
- date added to LUP
- 2016-04-01 10:34:55
- date last changed
- 2022-04-20 03:35:21
@article{ae348fa8-ae08-428d-9a7b-a5ffcb82d9ad,
abstract = {{Islet-level oxidative stress has been proposed as a trigger for type 1 diabetes (T1D), and release of cytokines by infiltrating immune cells further elevates reactive oxygen species (ROS), exacerbating beta cell duress. To identify genes/mechanisms involved with diabeto-genesis at the beta cell level, gene expression profiling and targeted follow-up studies were used to investigate islet activity in the biobreeding (BB) rat. Forty-day-old spontaneously diabetic lymphopenic BB DRlyp/lyp rats (before T cell insulitis) as well as nondiabetic BB DR+/+ rats, nondiabetic but lymphopenic F344lyp/lyp rats, and healthy Fischer (F344) rats were examined. Gene expression profiles of BB rat islets were highly distinct from F344 islets and under-expressed numerous genes involved in ROS metabolism, including glutathione S-transferase (GST) family members (Gstm2, Gstm4, Gstm7, Gstt1, Gstp1, and Gstk1), superoxide dismutases (Sod2 and Sod3), peroxidases, and peroxiredoxins. This pattern of under-expression was not observed in brain, liver, or muscle. Compared with F344 rats, BB rat pancreata exhibited lower GST protein levels, while plasma GST activity was found significantly lower in BB rats. Systemic administration of the antioxidant N-acetyl cysteine to DRlyp/lyp rats altered abundances of peripheral eosinophils, reduced severity of insulitis, and significantly delayed but did not prevent diabetes onset. We find evidence of b cell dysfunction in BB rats independent of T1D progression, which includes lower expression of genes related to antioxidative defense mechanisms during the pre-onset period that may contribute to overall T1D susceptibility.}},
author = {{Bogdani, Marika and Henschel, Angela M. and Kansra, Sanjay and Fuller, Jessica M. and Geoffrey, Rhonda and Jia, Shuang and Kaldunski, Mary L. and Pavletich, Scott and Prosser, Simon and Chen, Yi-Guang and Lernmark, Åke and Hessner, Martin J.}},
issn = {{1479-6805}},
language = {{eng}},
number = {{2}},
pages = {{111--123}},
publisher = {{Society for Endocrinology}},
series = {{Journal of Endocrinology}},
title = {{Biobreeding rat islets exhibit reduced antioxidative defense and N-acetyl cysteine treatment delays type 1 diabetes}},
url = {{http://dx.doi.org/10.1530/JOE-12-0385}},
doi = {{10.1530/JOE-12-0385}},
volume = {{216}},
year = {{2013}},
}