Evidence map›Paper›PMID 37834034›Full record

ArticleInternational journal of molecular sciences2023

Detrimental Actions of Chlorinated Nucleosides on the Function and Viability of Insulin-Producing Cells.

Inga Sileikaite-Morvaközi, William H Hansen, Michael J Davies, Thomas Mandrup-Poulsen, Clare L Hawkins

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Inga Sileikaite-MorvaköziDepartment of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.ORCID 0000-0003-0711-8215
William H HansenDepartment of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Michael J DaviesDepartment of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.ORCID 0000-0002-5196-6919
Thomas Mandrup-PoulsenDepartment of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.ORCID 0000-0002-3215-9273
Clare L HawkinsDepartment of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.ORCID 0000-0003-2738-5089

Funding

Danish Diabetes Academy PhD013-19Novo Nordisk Foundation NNF13OC0004294Novo Nordisk Foundation NNF17OC0028990Novo Nordisk Foundation NNF20SA0064214
6 · The paper itself

Abstract

Neutrophils are innate immune cells that play a key role in pathogen clearance. They contribute to inflammatory diseases, including diabetes, by releasing pro-inflammatory cytokines, reactive oxygen species, and extracellular traps (NETs). NETs contain a DNA backbone and catalytically active myeloperoxidase (MPO), which produces hypochlorous acid (HOCl). Chlorination of the DNA nucleoside 8-chloro-deoxyguanosine has been reported as an early marker of inflammation in diabetes. In this study, we examined the reactivity of different chlorinated nucleosides, including 5-chloro-(deoxy)cytidine (5ClC, 5CldC), 8-chloro-(deoxy)adenosine (8ClA, 8CldA) and 8-chloro-(deoxy)guanosine (8ClG, 8CldG), with the INS-1E β-cell line. Exposure of INS-1E cells to 5CldC, 8CldA, 8ClA, and 8CldG decreased metabolic activity and intracellular ATP, and, together with 8ClG, induced apoptotic cell death. Exposure to 8ClA, but not the other nucleosides, resulted in sustained endoplasmic reticulum stress, activation of the unfolded protein response, and increased expression of thioredoxin-interacting protein (TXNIP) and heme oxygenase 1 (HO-1). Exposure of INS-1E cells to 5CldC also increased TXNIP and NAD(P)H dehydrogenase quinone 1 (NQO1) expression. In addition, a significant increase in the mRNA expression of NQO1 and GPx4 was seen in INS-1E cells exposed to 8ClG and 8CldA, respectively. However, a significant decrease in intracellular thiols was only observed in INS-1E cells exposed to 8ClG and 8CldG. Finally, a significant decrease in the insulin stimulation index was observed in experiments with all the chlorinated nucleosides, except for 8ClA and 8ClG. Together, these results suggest that increased formation of chlorinated nucleosides during inflammation in diabetes could influence β-cell function and may contribute to disease progression.

Indexed as

Diabetes MellitusInsulin-Secreting CellsDNAHumansInflammationInsulinNucleosidesDNAInsulinNucleosideschlorinated nucleosidesdiabeteshypochlorous acidinflammationmyeloperoxidase

Identifiers

PMID37834034
PMCPMC10572493

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.