Evidence mapPaperPMID 39026321Full record

ArticleCardiovascular diabetology2024

In-depth phosphoproteomic profiling of the insulin signaling response in heart tissue and cardiomyocytes unveils canonical and specialized regulation.

Jonathan Samuel Achter, Estefania Torres Vega, Andrea Sorrentino, Konstantin Kahnert, Katrine Douglas Galsgaard, Pablo Hernandez-Varas, Michael Wierer, Jens Juul Holst, Jørgen Frank Pind Wojtaszewski, Robert William Mills and 2 more

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Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Beta-Adrenergic Stimulation andbioRxiv : the preprint server for biology · 2026
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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Jonathan Samuel Achter *Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Estefania Torres Vega *Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Andrea Sorrentino *Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Konstantin KahnertDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Katrine Douglas GalsgaardDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Pablo Hernandez-VarasCore Facility for Integrated Microscopy, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Michael WiererProteomics Research Infrastructure, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jens Juul HolstDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jørgen Frank Pind WojtaszewskiThe August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Robert William MillsDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Rasmus KjøbstedThe August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Alicia LundbyDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. alicia.lundby@sund.ku.dk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInsulin signaling regulates cardiac substrate utilization and is implicated in physiological adaptations of the heart. Alterations in the signaling response within the heart are believed to contribute to pathological conditions such as type-2 diabetes and heart failure. While extensively investigated in several metabolic organs using phosphoproteomic strategies, the signaling response elicited in cardiac tissue in general, and specifically in the specialized cardiomyocytes, has not yet been investigated to the same extent.

methodsInsulin or vehicle was administered to male C57BL6/JRj mice via intravenous injection into the vena cava. Ventricular tissue was extracted and subjected to quantitative phosphoproteomics analysis to evaluate the insulin signaling response. To delineate the cardiomyocyte-specific response and investigate the role of Tbc1d4 in insulin signal transduction, cardiomyocytes from the hearts of cardiac and skeletal muscle-specific Tbc1d4 knockout mice, as well as from wildtype littermates, were studied. The phosphoproteomic studies involved isobaric peptide labeling with Tandem Mass Tags (TMT), enrichment for phosphorylated peptides, fractionation via micro-flow reversed-phase liquid chromatography, and high-resolution mass spectrometry measurements.

resultsWe quantified 10,399 phosphorylated peptides from ventricular tissue and 12,739 from isolated cardiomyocytes, localizing to 3,232 and 3,128 unique proteins, respectively. In cardiac tissue, we identified 84 insulin-regulated phosphorylation events, including sites on the Insulin Receptor (Insr

conclusionWe present a first global outline of the insulin-induced phosphorylation signaling response in heart tissue and in isolated adult cardiomyocytes, detailing the specific residues with changed phosphorylation abundances. Our study marks an important step towards understanding the role of insulin signaling in cardiac diseases linked to insulin resistance.

Indexed as

InsulinMice, Inbred C57BLMice, KnockoutMyocytes, CardiacPhosphoproteinsProteomicsSignal TransductionAnimalsGTPase-Activating ProteinsMaleMicePhosphorylationProto-Oncogene Proteins c-aktReceptor, InsulinGTPase-Activating ProteinsInsulinPhosphoproteinsProto-Oncogene Proteins c-aktReceptor, InsulinCardiac signalingCardiometabolicInsulin resistanceInsulin signalingKinaseMetabolismPhosphoproteomicsPhosphorylationProteomicsTbc1d4

Identifiers

PMID39026321
PMCPMC11264841

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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.