Evidence map›Paper›PMID 33667344›Full record

ArticleDevelopmental cell2021

Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes.

Wendy M McKimpson, Yun Chen, James A Irving, Min Zheng, Jeremy Weinberger, Wilson Lek Wen Tan, Zenia Tiang, Alistair M Jagger, Streamson C Chua, Jeffrey E Pessin and 3 more

Open access · greenAbstract read
In one paragraph

Article in Developmental cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 7 institutions in 3 countries.

Wendy M McKimpsonDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Yun ChenDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
James A IrvingUCL Respiratory Medicine, University College London, London WC1E 6BN, UK; Institute of Structural and Molecular Biology/Birkbeck, University of London, London WC1E 7HX, UK.
Min ZhengDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Jeremy WeinbergerDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Wilson Lek Wen TanCardiovascular Research Institute, National University Health Systems, Singapore, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Zenia TiangCardiovascular Research Institute, National University Health Systems, Singapore, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Alistair M JaggerUCL Respiratory Medicine, University College London, London WC1E 6BN, UK; Institute of Structural and Molecular Biology/Birkbeck, University of London, London WC1E 7HX, UK.
Streamson C ChuaDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Jeffrey E PessinDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Roger S-Y FooCardiovascular Research Institute, National University Health Systems, Singapore, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
David A LomasUCL Respiratory Medicine, University College London, London WC1E 6BN, UK; Institute of Structural and Molecular Biology/Birkbeck, University of London, London WC1E 7HX, UK.
Richard N KitsisDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: richard.kitsis@einsteinmed.org.
Albert Einstein College of Medicine · USAgency for Science, Technology and Research · SGBirkbeck, University of London · GBGenome Institute of Singapore · SGInstitute of Structural and Molecular Biology · GBNational University Health System · SGUniversity College London · GB

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI STEVEN C. ALMO · 1985 to 2026
$111.2M
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7M
TRAINING PROGRAM IN CELLULAR &MOLEC. BIOLOGY &GENETICST32GM007491 · NIGMS · YESHIVA UNIVERSITY · PI QUERY, CHARLES C · 1985 to 2021
$17.0M
REGULATION OF THE INSULIN RECEPTOR KINASER01DK033823 · NIDDK · UNIVERSITY OF IOWA · PI KURLAND, IRWIN JACK, PESSIN, JEFFREY E. · 1986 to 2022
$6.7M
CARDIAC MYOCYTE APOPTOSIS--MECHANISM AND SIGNIFICANCER01HL060665 · NHLBI · YESHIVA UNIVERSITY · PI KITSIS, RICHARD N · 1998 to 2013
$5.3M
Gut cell plasticity during diabetes treatmentK01DK121873 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MCKIMPSON, WENDY MARIE · 2019 to 2022
$612k
Medical Research Council N024842/1NCI NIH HHS P30 CA013330NHLBI NIH HHS R01 HL060665NIDDK NIH HHS K01 DK121873NIDDK NIH HHS P30 DK020541NIDDK NIH HHS R01 DK033823NIGMS NIH HHS T32 GM007491
6 · The paper itself

Abstract

Loss of insulin-secreting pancreatic β cells through apoptosis contributes to the progression of type 2 diabetes, but underlying mechanisms remain elusive. Here, we identify a pathway in which the cell death inhibitor ARC paradoxically becomes a killer during diabetes. While cytoplasmic ARC maintains β cell viability and pancreatic architecture, a pool of ARC relocates to the nucleus to induce β cell apoptosis in humans with diabetes and several pathophysiologically distinct mouse models. β cell death results through the coordinate downregulation of serpins (serine protease inhibitors) not previously known to be synthesized and secreted by β cells. Loss of the serpin α

Indexed as

Apoptosisalpha 1-AntitrypsinAnimalsApoptosis Regulatory ProteinsCell NucleusCytoplasmCytoskeletal ProteinsDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2FemaleHumansInsulin-Secreting CellsMaleMiceMice, Inbred C57BLMice, Knockoutactivity regulated cytoskeletal-associated proteinalpha 1-AntitrypsinApoptosis Regulatory ProteinsCytoskeletal ProteinsMuscle ProteinsNerve Tissue ProteinsNol3 protein, mousealpha-1 antitrypsinARCcell deathdiabetesserpins

Identifiers

PMID33667344
PMCPMC8146085
OpenAlexW3134737164

What OpenQuestion holds

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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.