Evidence map›Paper›PMID 40829182›Full record

ArticleThe Journal of clinical investigation2025

SEC61B regulates calcium flux and platelet hyperreactivity in diabetes.

Yvonne X Kong, Rajan Rehan, Cesar L Moreno, Søren Madsen, Yunwei Zhang, Huiwen Zhao, Miao Qi, Callum B Houlahan, Siân P Cartland, Declan Robertshaw and 25 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Redox Control in Platelet Activity and Therapy.Antioxidants (Basel, Switzerland) · 2025
    Review
  5. Article
  6. Enhancer regulation in cancer: from epigenetics to mArchives of pharmacal research · 2025
    Review
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

35 authors.

Yvonne X KongCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Rajan RehanCentral Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Cesar L MorenoCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Søren MadsenCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Yunwei ZhangCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Huiwen ZhaoCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Miao QiCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Callum B HoulahanCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Siân P CartlandHeart Research Institute, University of Sydney, Sydney, New South Wales, Australia.
Declan RobertshawCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Vincent TrangCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Frederick Jun Liang OngCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Michael LiuCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Edward ChengCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Imala AlwisCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Alexander DupuyCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Michelle CieleshCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Kristen C CookeCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Meg PotterCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Jacqueline StöckliCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Grant MorahanCentre for Diabetes Research, Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia.
Maggie L Kalev-ZylinskaDepartment of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
Matthew T RondinaMolecular Medicine Program, Department of Internal Medicine, and Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, Utah, USA.
Sol SchulmanDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Jean Y H YangCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
G Gregory NeelyCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Simone M SchoenwaelderCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Shaun P JacksonCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
David E JamesCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Mary M KavurmaHeart Research Institute, University of Sydney, Sydney, New South Wales, Australia.
Samantha L HockingCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Stephen M TwiggCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
James C WeaverCentral Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Mark LaranceCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Freda H PassamCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Platelet hyperreactivity increases the risk of cardiovascular thrombosis in diabetes and failure of antiplatelet drug therapies. Elevated basal and agonist-induced calcium flux is a fundamental cause of platelet hyperreactivity in diabetes; however, the mechanisms responsible for this remain largely unknown. Using a high-sensitivity, unbiased proteomic platform, we consistently detected over 2,400 intracellular proteins and identified proteins that were differentially released by platelets in type 2 diabetes. We identified that SEC61 translocon subunit β (SEC61B) was increased in platelets from humans and mice with hyperglycemia and in megakaryocytes from mice with hyperglycemia. SEC61 is known to act as an endoplasmic reticulum (ER) calcium leak channel in nucleated cells. Using HEK293 cells, we showed that SEC61B overexpression increased calcium flux into the cytosol and decreased protein synthesis. Concordantly, platelets in hyperglycemic mice mobilized more calcium and had decreased protein synthesis. Platelets in both humans and mice with hyperglycemia had increased ER stress. ER stress induced the expression of platelet SEC61B and increased cytosolic calcium. Inhibition of SEC61 with anisomycin decreased platelet calcium flux and inhibited platelet aggregation in vitro and in vivo. These studies demonstrate the existence of a mechanism whereby ER stress-induced upregulation of platelet SEC61B leads to increased cytosolic calcium, potentially contributing to platelet hyperreactivity in diabetes.

Indexed as

Blood PlateletsCalciumCalcium SignalingDiabetes Mellitus, Type 2SEC Translocation ChannelsAnimalsDiabetes Mellitus, ExperimentalEndoplasmic Reticulum StressHEK293 CellsHumansHyperglycemiaMaleMicePlatelet AggregationCalciumSEC Translocation ChannelsCalcium channelsCardiologyCell biologyHematologyPlateletsProteomics

Identifiers

PMID40829182
PMCPMC12352904

What OpenQuestion holds

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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 OpenQuestion graph.