Evidence map›Paper›PMID 36198264›Full record

ArticleCell reports2022

E2F1 transcription factor mediates a link between fat and islets to promote β cell proliferation in response to acute insulin resistance.

Jun Shirakawa, Yu Togashi, Giorgio Basile, Tomoko Okuyama, Ryota Inoue, Megan Fernandez, Mayu Kyohara, Dario F De Jesus, Nozomi Goto, Wei Zhang and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

10 citing papers in PubMed, 25 citations in OpenAlex.

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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

18 authors at 4 institutions in 3 countries.

Jun ShirakawaIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA; Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi 3718512, Japan; Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, Yokohama 2360004, Japan. Electronic address: jshira@gunma-u.ac.jp.
Yu TogashiDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, Yokohama 2360004, Japan.
Giorgio BasileIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA.
Tomoko OkuyamaDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, Yokohama 2360004, Japan.
Ryota InoueLaboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi 3718512, Japan.
Megan FernandezIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA.
Mayu KyoharaDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, Yokohama 2360004, Japan.
Dario F De JesusIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA.
Nozomi GotoDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, Yokohama 2360004, Japan.
Wei ZhangIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA.
Takahiro TsunoLaboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi 3718512, Japan.
Tatsuya KinClinical Islet Laboratory and Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada.
Hui PanBioinformatics Core, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Jonathan M DreyfussBioinformatics Core, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
A M James ShapiroClinical Islet Laboratory and Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada.
Peng YiIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA.
Yasuo TerauchiDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, Yokohama 2360004, Japan.
Rohit N KulkarniIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: rohit.kulkarni@joslin.harvard.edu.
Joslin Diabetes Center · USYokohama City University · JPGunma University · JPUniversity of Alberta · CA

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Role of IGF-1 and Insulin Receptors Beta-Cell SurvivalR01DK067536 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 2004 to 2026
$8.0M
Validation of small molecule 12-lipoxygenase inhibitors in metabolic diseaseR01DK105588 · NIDDK · UNIVERSITY OF CHICAGO · PI KULKARNI, ROHIT N., MIRMIRA, RAGHAVENDRA G · 2015 to 2024
$5.5M
Interplay Between SERPINB1 and TLR2/TLR4 in Beta Cell RegenerationR01DK117639 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ARVAN, PETER, KULKARNI, ROHIT N. · 2019 to 2023
$3.0M
NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK067536NIDDK NIH HHS R01 DK105588NIDDK NIH HHS R01 DK117639
6 · The paper itself

Abstract

Prevention or amelioration of declining β cell mass is a potential strategy to cure diabetes. Here, we report the pathways utilized by β cells to robustly replicate in response to acute insulin resistance induced by S961, a pharmacological insulin receptor antagonist. Interestingly, pathways that include CENP-A and the transcription factor E2F1 that are independent of insulin signaling and its substrates appeared to mediate S961-induced β cell multiplication. Consistently, pharmacological inhibition of E2F1 blocks β-cell proliferation in S961-injected mice. Serum from S961-treated mice recapitulates replication of β cells in mouse and human islets in an E2F1-dependent manner. Co-culture of islets with adipocytes isolated from S961-treated mice enables β cells to duplicate, while E2F1 inhibition limits their growth even in the presence of adipocytes. These data suggest insulin resistance-induced proliferative signals from adipocytes activate E2F1, a potential therapeutic target, to promote β cell compensation.

Indexed as

Insulin ResistanceInsulin-Secreting CellsAnimalsCell ProliferationCentromere Protein AE2F1 Transcription FactorHumansInsulinMiceMice, KnockoutReceptor, InsulinCentromere Protein AE2F1 protein, humanE2f1 protein, mouseE2F1 Transcription FactorInsulinReceptor, Insulinacute insulin resistanceadipocytescompensationCP: MetabolismE2F1human beta cellsinsulin receptorinter-organ communicationtranscription factorβ cell proliferation

Identifiers

PMID36198264
PMCPMC9617565
OpenAlexW4301394809

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.