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Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish

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Title: Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish
Authors: Janjuha, S
Singh, SP
Tsakmaki, A
Mousavy Gharavy, NS
Murawala, P
Konantz, J
Birke, S
Hodson, DJ
Rutter, GA
Bewick, GA
Item Type: Journal Article
Abstract: The pancreatic islet, a cellular community harboring the insulin-producing beta-cells, is known to undergo age-related alterations. However, only a handful of signals associated with aging have been identified. By comparing beta-cells from younger and older zebrafish, here we show that the aging islets exhibit signs of chronic inflammation. These include recruitment of tnfα-expressing macrophages and the activation of NF-kB signaling in beta-cells. Using a transgenic reporter, we show that NF-kB activity is undetectable in juvenile beta-cells, whereas cells from older fish exhibit heterogeneous NF-kB activity. We link this heterogeneity to differences in gene expression and proliferation. Beta-cells with high NF-kB signaling proliferate significantly less compared to their neighbors with low activity. The NF-kB signalinghi cells also exhibit premature upregulation of socs2, an age-related gene that inhibits beta-cell proliferation. Together, our results show that NF-kB activity marks the asynchronous decline in beta-cell proliferation with advancing age.
Issue Date: 6-Apr-2018
Date of Acceptance: 6-Apr-2018
URI: http://hdl.handle.net/10044/1/58916
DOI: https://dx.doi.org/10.7554/eLife.32965
ISSN: 2050-084X
Publisher: eLife Sciences Publications Ltd
Journal / Book Title: eLife
Volume: 7
Copyright Statement: © 2018 Janjuha et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
ENDOPLASMIC-RETICULUM STRESS
LARGE GENE LISTS
IN-VIVO
LIFE
REPLICATION
ACTIVATION
APOPTOSIS
SURVIVAL
PATHWAY
GLUCOSE
Diabetes
Inflammation
NF-kB
beta-cells
cell biology
pancreas
zebrafish
Publication Status: Published
Article Number: e32965
Appears in Collections:Department of Medicine
Faculty of Medicine



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