Evidence map›Paper›PMID 34823065›Full record

ArticleMolecular metabolism2022

Deletion of ABCB10 in beta-cells protects from high-fat diet induced insulin resistance.

Michael Shum, Mayuko Segawa, Raffi Gharakhanian, Ana Viñuela, Matthew Wortham, Siyouneh Baghdasarian, Dane M Wolf, Samuel B Sereda, Laura Nocito, Linsey Stiles and 5 more

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

Article in Molecular metabolism, 2022. 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
–field-weighted citation impact, top 73% 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, 3 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
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

15 authors at 4 institutions in 3 countries.

Michael ShumDepartment of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA; Department of Molecular Medicine, Faculty of Medicine, Universite Laval, Quebec City G1V 0A6, Canada. Electronic address: michael.shum@crchudequebec.ulaval.ca.
Mayuko SegawaDepartment of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA.
Raffi GharakhanianDepartment of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA.
Ana ViñuelaBioscience Institute, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, United Kingdom.
Matthew WorthamDepartments of Pediatrics and Cellular & Molecular Medicine, Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA 92093, USA.
Siyouneh BaghdasarianDepartment of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA.
Dane M WolfDepartment of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA; Evans Biomedical Research Center, Boston University School of Medicine, 650 Albany St., Boston, MA, 02118, USA.
Samuel B SeredaEvans Biomedical Research Center, Boston University School of Medicine, 650 Albany St., Boston, MA, 02118, USA.
Laura NocitoEvans Biomedical Research Center, Boston University School of Medicine, 650 Albany St., Boston, MA, 02118, USA.
Linsey StilesDepartment of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA.
Zhiqiang ZhouDepartment of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA.
Vincent GutierrezDepartment of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA; Molecular and Cellular Integrative Physiology, UCLA, 612 Charles E. Young Dr., Los Angeles, CA 90095, USA.
Maike SanderDepartments of Pediatrics and Cellular & Molecular Medicine, Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA 92093, USA.
Orian S ShirihaiDepartment of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA; Molecular and Cellular Integrative Physiology, UCLA, 612 Charles E. Young Dr., Los Angeles, CA 90095, USA.
Marc LiesaDepartment of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr., Los Angeles, CA 90095, USA; Molecular and Cellular Integrative Physiology, UCLA, 612 Charles E. Young Dr., Los Angeles, CA 90095, USA; Molecular Biology Institute at UCLA, 611 Charles E. Young Dr., Los Angeles, CA 90095, USA. Electronic address: mliesa@mednet.ucla.edu.
University of California, Los Angeles · USBoston University · USUniversity of California San Diego · USCentre for Life · GB

Funding

Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILES Frome WILKINSON · 2003 to 2026
$40.4M
Transgenic CoreP30DK046200 · NIDDK · TUFTS MEDICAL CENTER · PI HU, FRANK B · 1992 to 2021
$25.0M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Nkx6 gene function in pancreas developmentR01DK068471 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI WORTHAM, MATTHEW · 2004 to 2024
$6.6M
Novel insights into nutrient-dependent regulation of beta cell proliferationR01DK078803 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SANDER, MAIKE · 2007 to 2022
$4.4M
Role of the heme-related mitochondrial antioxidant ABCB10 in alcoholic liver diseaseR01AA026914 · NIAAA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SHIRIHAI, ORIAN S · 2019 to 2022
$1.4M
NIAAA NIH HHS R01 AA026914NIDDK NIH HHS P30 DK041301NIDDK NIH HHS P30 DK046200NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK068471NIDDK NIH HHS R01 DK078803
6 · The paper itself

Abstract

objectiveThe contribution of beta-cell dysfunction to type 2 diabetes (T2D) is not restricted to insulinopenia in the late stages of the disease. Elevated fasting insulinemia in normoglycemic humans is a major factor predicting the onset of insulin resistance and T2D, demonstrating an early alteration of beta-cell function in T2D. Moreover, an early and chronic increase in fasting insulinemia contributes to insulin resistance in high-fat diet (HFD)-fed mice. However, whether there are genetic factors that promote beta-cell-initiated insulin resistance remains undefined. Human variants of the mitochondrial transporter ABCB10, which regulates redox by increasing bilirubin synthesis, have been associated with an elevated risk of T2D. The effects of T2D ABCB10 variants on ABCB10 expression and the actions of ABCB10 in beta-cells are unknown.

methodsThe expression of beta-cell ABCB10 was analyzed in published transcriptome datasets from human beta-cells carrying the T2D-risk ABCB10 variant. Insulin sensitivity, beta-cell proliferation, and secretory function were measured in beta-cell-specific ABCB10 KO mice (Ins1

resultsCarrying the T2Drisk allele G of ABCB10 rs348330 variant was associated with increased ABCB10 expression in human beta-cells. Constitutive deletion of Abcb10 in beta-cells protected mice from hyperinsulinemia and insulin resistance by limiting HFD-induced beta-cell expansion. An early limitation in GSIS and H

conclusionsBeta-cell ABCB10 is required for HFD to induce insulin resistance in mice by amplifying beta-cell mass expansion to maladaptive levels that cause fasting hyperinsulinemia.

Indexed as

AnimalsATP-Binding Cassette TransportersBlood GlucoseDiabetes Mellitus, Type 2Diet, High-FatFemaleGlucoseGlucose Tolerance TestInsulinInsulin ResistanceInsulin-Secreting CellsInsulin SecretionIslets of LangerhansMaleMiceMice, Inbred C57BLAbcb10 protein, mouseATP-Binding Cassette TransportersBlood GlucoseGlucoseInsulinABCB10Beta-cellInsulin resistanceMitochondria

Identifiers

PMID34823065
PMCPMC8689243
OpenAlexW3215165618

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.