Evidence map›Paper›PMID 30833468›Full record

ArticleDiabetes2019

DNA Damage Does Not Cause BrdU Labeling of Mouse or Human β-Cells.

Rohit B Sharma, Christine Darko, Xiaoying Zheng, Brian Gablaski, Laura C Alonso

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

13 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
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  7. Article
  8. Effects of Heme Oxygenase-1 on c-Kit-Positive Cardiac Cells.International journal of molecular sciences · 2021
    Article
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  10. Review
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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 at 1 institution in 1 country.

Rohit B SharmaDiabetes Center of Excellence in the Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
Christine DarkoDiabetes Center of Excellence in the Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
Xiaoying ZhengDiabetes Center of Excellence in the Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
Brian GablaskiDiabetes Center of Excellence in the Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
Laura C AlonsoDiabetes Center of Excellence in the Department of Medicine, University of Massachusetts Medical School, Worcester, MA laura.alonso@umassmed.edu.ORCID 0000-0001-5056-8970
University of Massachusetts Chan Medical School · US

Funding

The Human Islet Distribution Coordinating Center (UC4)UC4DK098085 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI EVANS-MOLINA, CARMELLA, NILAND, JOYCE CAROL · 2012 to 2017
$25.6M
Integrated Islet Distribution Program (U24) - 2021U24DK098085 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Carmella Evans-Molina, Joyce Carol Niland · 2021 to 2026
$17.8M
Free Fatty Acids, p16 and Pancreatic Beta Cell ProliferationR01DK095140 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ALONSO, LAURA C · 2012 to 2016
$1.9M
Role of GRP78 in beta cell adaptation in obesity and diabetesR01DK113300 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI ALONSO, LAURA C · 2018 to 2021
$1.7M
ATF6 and the Beta CellR01DK114686 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI ALONSO, LAURA C · 2017 to 2019
$1.5M
NIDDK NIH HHS R01 DK095140NIDDK NIH HHS R01 DK113300NIDDK NIH HHS R01 DK114686NIDDK NIH HHS U24 DK098085NIDDK NIH HHS UC4 DK098085
6 · The paper itself

Abstract

Pancreatic β-cell regeneration, the therapeutic expansion of β-cell number to reverse diabetes, is an important goal. Replication of differentiated insulin-producing cells is the major source of new β-cells in adult mice and juvenile humans. Nucleoside analogs such as BrdU, which are incorporated into DNA during S-phase, have been widely used to quantify β-cell proliferation. However, reports of β-cell nuclei labeling with both BrdU and γ-phosphorylated H2A histone family member X (γH2AX), a DNA damage marker, have raised questions about the fidelity of BrdU to label S-phase, especially during conditions when DNA damage is present. We performed experiments to clarify the causes of BrdU-γH2AX double labeling in mouse and human β-cells. BrdU-γH2AX colabeling is neither an age-related phenomenon nor limited to human β-cells. DNA damage suppressed BrdU labeling and BrdU-γH2AX colabeling. In dispersed islet cells, but not in intact islets or in vivo, pro-proliferative conditions promoted both BrdU and γH2AX labeling, which could indicate DNA damage, DNA replication stress, or cell cycle-related intrinsic H2AX phosphorylation. Strategies to increase β-cell number must not only tackle the difficult challenge of enticing a quiescent cell to enter the cell cycle, but also achieve safe completion of the cell division process.

Indexed as

AnimalsApoptosisBromodeoxyuridineCell CycleCell ProliferationDNADNA DamageHumansInsulin-Secreting CellsMiceBromodeoxyuridineDNA

Identifiers

PMID30833468
PMCPMC6477907
OpenAlexW2920422382

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.