Evidence map›Paper›PMID 40291746›Full record

ArticlebioRxiv : the preprint server for biology2025

Immunomodulation by AZD1656 reverses cardiac dysfunction, metabolic remodelling and reduces infarct size in type 2 diabetic cardiomyopathy.

Stephanie Anderson, Anja Karlstaedt, Jianmin Chen, Caroline E O'Riordan, Michael R Barnes, Zorana Štaka, Lauren J Albee, Conor Garrod-Ketchley, Sanushi Thamasha Dambure Vithanachchi, Hiran A Prag and 8 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Stephanie AndersonDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Anja KarlstaedtDepartment of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, USA.
Jianmin ChenWilliam Harvey Research Institute, Bart's and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
Caroline E O'RiordanWilliam Harvey Research Institute, Bart's and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
Michael R BarnesWilliam Harvey Research Institute, Bart's and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
Zorana ŠtakaWilliam Harvey Research Institute, Bart's and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
Lauren J AlbeeSchool of Cardiovascular Science and Medicine, The Rayne Institute, St Thomas Hospital, King's College London, London, UK.
Conor Garrod-KetchleyWilliam Harvey Research Institute, Bart's and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
Sanushi Thamasha Dambure VithanachchiWilliam Harvey Research Institute, Bart's and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
Hiran A PragMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.ORCID 0000-0002-4753-8567
Filip CvetkoMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
Christoph ThiemermannWilliam Harvey Research Institute, Bart's and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
Andrew Jm LewisDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Michael P MurphyMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
David M SmithEmerging Innovation Unit, Discovery Sciences, R&D, AstraZeneca, Cambridge, UK.
Sian M HensonWilliam Harvey Research Institute, Bart's and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.ORCID 0000-0003-1893-4912
Damian J TylerDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Dunja AksentijevicWilliam Harvey Research Institute, Bart's and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.ORCID 0000-0002-8480-6727

Funding

Regulation of cardiac metabolism during LeukemiaR01HL177461 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI Anja Karlstaedt · 2025 to 2026
$1.1M
Metabolic Rewiring of the Heart Through Reductive CarboxylationR00HL141702 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI KARLSTAEDT, ANJA · 2021 to 2023
$747k
NHLBI NIH HHS R00 HL141702NHLBI NIH HHS R01 HL177461Wellcome Trust
6 · The paper itself

Abstract

Type 2 Diabetes (T2D) can lead to diabetic cardiomyopathy (dbCM), which is characterised by chronic, systemic inflammation, disrupted metabolism and impaired cardiac function. However, whether cardiac inflammation is present in dbCM and causally linked to metabolic remodelling remains unknown. AZD1656 (AZD), an activator of glucokinase, was postulated to provide glycaemic control in T2D by acting on in the pancreas and liver. However, AZD failed to control hyperglycaemia in clinical trials. Nevertheless, testing of the drug in COVID-19 T2D patients as part of the ARCADIA trial indicated an immunomodulatory effect. Therefore, we used the db/db mouse model of dbCM and an integrated in vivo and ex vivo experimental approach to examine the effects of AZD on cardiac functional and metabolic disturbances and inflammation. 20-week db/db mice displaying the features of human dbCM (obesity, hyperglycaemia and diastolic dysfunction) treated for six weeks with AZD showed improved metabolic remodelling, attenuated diastolic dysfunction, reduced infarct size and improved functional post-ischemic recovery compared to untreated dbCM, alongside an improved cardiac immunophenotype, including reduced T cell-mediated fibrosis and B cell infiltration. Therefore, targeting of immunometabolism may offer a new therapeutic approach to treat cardiac dysfunction and metabolic dysregulation and reduce infarct size in dbCM.

Indexed as

cardio-immunologyinflammationmetabolic remodellingtype 2 diabetestype 2 diabetic cardiomyopathy

Identifiers

PMID40291746
PMCPMC12027331

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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 OpenQuestion graph.