Evidence map›Paper›PMID 32882164›Full record

ArticleCell metabolism2020

A Membrane-Bound Diacylglycerol Species Induces PKCϵ-Mediated Hepatic Insulin Resistance.

Kun Lyu, Ye Zhang, Dongyan Zhang, Mario Kahn, Kasper W Ter Horst, Marcos R S Rodrigues, Rafael C Gaspar, Sandro M Hirabara, Panu K Luukkonen, Seohyuk Lee and 9 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Cell metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05597709 (Prevalence of Metabolic Associated Fatty Liver Disease in Patients With Type 2 Diabetes in Jiangsu Province of China), which is not on this map. Cited by 107 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 3 pooled it
9.7field-weighted citation impact, top 1% 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.

NCT05597709 recruitingnot on this mapstarted 2022, after this paper: background citation

Prevalence of Metabolic Associated Fatty Liver Disease in Patients With Type 2 Diabetes in Jiangsu Province of China: a Prospective, Multicenter, Real-world Study

TypeobservationalSponsorWuxi Hisky Medical Technology Co LtdRan2022 to 2027Enrolled2,900ConditionsType 2 Diabetes Mellitus in Remission, Metabolic Associated Fatty Liver DiseaseArmsUltrasound attenuation parameter measurement, fasting blood glucose and fasting insulin determination
3 · Its place in the literature

Who cites it

107 citing papers in PubMed, 3 syntheses or guidelines pooled it, 144 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Review
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  9. Article
  10. Exercise and Fat: A Primer.Sports medicine - open · 2026
    Review
  11. Article
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  16. Article
  17. Insulin receptorNature communications · 2026
    Article
  18. Article
  19. Review
  20. Article

47 more citing papers are in PubMed but not listed here.

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

19 authors at 7 institutions in 4 countries.

Kun LyuDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA.
Ye ZhangDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Endocrinology & Metabolism, First Hospital of Jilin University, Changchun, Jilin 130021, China.
Dongyan ZhangDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
Mario KahnDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
Kasper W Ter HorstDepartment of Endocrinology and Metabolism Amsterdam University Medical Center, 1105AZ Amsterdam, the Netherlands.
Marcos R S RodriguesDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; School of Medicine, State University of Ponta Grossa, Avenida General Carlos Cavalcanti, Ponta Grossa, PR 84030-900, Brazil.
Rafael C GasparDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Laboratory of Molecular Biology of Exercise, School of Applied Science, University of Campinas, Limeira, SP 13484-350, Brazil.
Sandro M HirabaraDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Postgraduate Interdisciplinary Program of Health Sciences, Cruzeiro do Sul University, Sao Paulo, SP 01506-000, Brazil.
Panu K LuukkonenDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
Seohyuk LeeDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
Sanjay BhanotIonis Pharmaceuticals, Carlsbad, CA 92008, USA.
Jesse RinehartDepartment of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA; Systems Biology Institute, Yale University, West Haven, CT 06516, USA.
Niels BlumeCV Research, Novo Nordisk A/S, Novo Nordisk Park, 2760 Maaloev, Denmark.
Morten Grønbech RaschAntibody Technology, Novo Nordisk A/S, Novo Nordisk Park, 2760 Maaloev, Denmark.
Mireille J SerlieDepartment of Endocrinology and Metabolism Amsterdam University Medical Center, 1105AZ Amsterdam, the Netherlands.
Jonathan S BoganDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Cell Biology, Yale School of Medicine, New Haven, CT 06510, USA.
Gary W ClineDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
Varman T SamuelDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; VA Connecticut Healthcare System, West Haven, CT 06516, USA.
Gerald I ShulmanDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: gerald.shulman@yale.edu.
Yale University · USNovo Nordisk (Denmark) · DKIonis Pharmaceuticals (United States) · USJilin University · CNUniversidade Cruzeiro do Sul · BRUniversidade Estadual de Ponta Grossa · BRVA Connecticut Healthcare System · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI Kevan C Herold, GERALD I SHULMAN · 1993 to 2026
$44.0M
Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI YASUKO IWAKIRI · 1986 to 2026
$31.1M
Effects of Hepatic Acetyl-CoA Carboxylase Inhibition on NAFLD and Hepatic Insulin ResistanceR01DK113984 · NIDDK · YALE UNIVERSITY · PI SHULMAN, GERALD I · 2017 to 2021
$3.7M
Development of Controlled Release Mitochondrial Protonophore (CRMP) as a Novel Treatment for Type-2 Diabetes and Non-Alcoholic Steatohepatitis in Dysmetabolic Non-Human PrimatesR01DK119968 · NIDDK · YALE UNIVERSITY · PI SHULMAN, GERALD I · 2019 to 2024
$2.7M
Microbiome origins and insulin regulatory responses of the short chain fatty acid acetateR01DK114793 · NIDDK · YALE UNIVERSITY · PI GOODMAN, ANDREW L, SHULMAN, GERALD I · 2018 to 2021
$2.4M
Vesicle Translocation and the Metabolic SyndromeR01DK092661 · NIDDK · YALE UNIVERSITY · PI BOGAN, JONATHAN · 2012 to 2018
$2.0M
Glucagon Regulation of Hepatic Mitochondrial Activity and Glucose Metabolism by InsP3R-1R01DK116774 · NIDDK · YALE UNIVERSITY · PI SHULMAN, GERALD I · 2018 to 2021
$1.7M
Cellular mechanisms for increased gluconeogenesis in type 2 diabetes mellitus: the role of lipid induced pyruvate carboxylase acetylation in increasing hepatic gluconeogenic capacity.I01BX000901 · VA · VA CONNECTICUT HEALTHCARE SYSTEM · PI SAMUEL, VARMAN T · 2012 to 2020
–
BLRD VA I01 BX000901NCATS NIH HHS UL1 TR001863NIDDK NIH HHS P30 DK034989NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK092661NIDDK NIH HHS R01 DK113984NIDDK NIH HHS R01 DK114793NIDDK NIH HHS R01 DK116774NIDDK NIH HHS R01 DK119968
6 · The paper itself

Abstract

Nonalcoholic fatty liver disease is strongly associated with hepatic insulin resistance (HIR); however, the key lipid species and molecular mechanisms linking these conditions are widely debated. We developed a subcellular fractionation method to quantify diacylglycerol (DAG) stereoisomers and ceramides in the endoplasmic reticulum (ER), mitochondria, plasma membrane (PM), lipid droplets, and cytosol. Acute knockdown (KD) of diacylglycerol acyltransferase-2 in liver induced HIR in rats. This was due to PM sn-1,2-DAG accumulation, which promoted PKCϵ activation and insulin receptor kinase (IRK)-T1160 phosphorylation, resulting in decreased IRK-Y1162 phosphorylation. Liver PM sn-1,2-DAG content and IRK-T1160 phosphorylation were also higher in humans with HIR. In rats, liver-specific PKCϵ KD ameliorated high-fat diet-induced HIR by lowering IRK-T1160 phosphorylation, while liver-specific overexpression of constitutively active PKCϵ-induced HIR by promoting IRK-T1160 phosphorylation. These data identify PM sn-1,2-DAGs as the key pool of lipids that activate PKCϵ and that hepatic PKCϵ is both necessary and sufficient in mediating HIR.

Indexed as

AnimalsCell MembraneDiglyceridesHumansInsulin ResistanceLiverMalePhosphorylationProtein Kinase C-epsilonRatsRats, Sprague-DawleyReceptor, Insulin1,2-diacylglycerolDiglyceridesProtein Kinase C-epsilonReceptor, Insulinceramidesdicylglycerolshepatic glucose productionhepatic glycogen synthesishepatic insulin resistanceinsulin receptor phosphorylationliquid chromatography-tandem mass spectrometrynonalcoholic fatty liver diseaseprotein kinase C-epsilontype 2 diabetes

Identifiers

PMID32882164
PMCPMC7544641
OpenAlexW3081770539

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Registered trials

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.