Evidence map›Paper›PMID 33618724›Full record

ArticleCardiovascular diabetology2021

Activation of the cardiac non-neuronal cholinergic system prevents the development of diabetes-associated cardiovascular complications.

Eng Leng Saw, James T Pearson, Daryl O Schwenke, Pujika Emani Munasinghe, Hirotsugu Tsuchimochi, Shruti Rawal, Sean Coffey, Philip Davis, Richard Bunton, Isabelle Van Hout and 5 more

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

Article in Cardiovascular diabetology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

19 citing papers in PubMed, 38 citations in OpenAlex.

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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.

Eng Leng SawDepartment of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, 270, Great King Street, Dunedin, 9016, New Zealand.
James T PearsonDepartment of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.ORCID 0000-0002-3318-5406
Daryl O SchwenkeDepartment of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, 270, Great King Street, Dunedin, 9016, New Zealand.
Pujika Emani MunasingheDepartment of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, 270, Great King Street, Dunedin, 9016, New Zealand.
Hirotsugu TsuchimochiDepartment of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.
Shruti RawalDepartment of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, 270, Great King Street, Dunedin, 9016, New Zealand.
Sean CoffeyDepartment of Medicine, School of Medicine, University of Otago, Dunedin, New Zealand.
Philip DavisDepartment of Cardiothoracic Surgery, School of Medicine, University of Otago, Dunedin, New Zealand.
Richard BuntonDepartment of Cardiothoracic Surgery, School of Medicine, University of Otago, Dunedin, New Zealand.
Isabelle Van HoutDepartment of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, 270, Great King Street, Dunedin, 9016, New Zealand.
Yuko KaiDepartment of Bioregulatory Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Michael J A WilliamsDepartment of Medicine, School of Medicine, University of Otago, Dunedin, New Zealand.
Yoshihiko Kakinuma *Department of Bioregulatory Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. k12417853@nms.ac.jp.
Martin Fronius *Department of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, 270, Great King Street, Dunedin, 9016, New Zealand. martin.fronius@otago.ac.nz.ORCID 0000-0002-3553-7786
Rajesh Katare *Department of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, 270, Great King Street, Dunedin, 9016, New Zealand. rajesh.katare@otago.ac.nz.ORCID 0000-0001-5419-7935
University of Otago · NZNippon Medical School · JPAustralian Regenerative Medicine Institute · AUNational Cerebral and Cardiovascular Center · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAcetylcholine (ACh) plays a crucial role in the function of the heart. Recent evidence suggests that cardiomyocytes possess a non-neuronal cholinergic system (NNCS) that comprises of choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), acetylcholinesterase (AChE) and type-2 muscarinic ACh receptors (M

methodsVentricular samples from type-2 diabetic humans and db/db mice were used to measure the expression pattern of NNCS components (ChAT, CHT1, VAChT, AChE and M

resultsImmunoblot analysis revealed alterations in the components of cardiac NNCS and GLUT-4 in the type-2 diabetic human and db/db mouse hearts. Interestingly, the dysregulation of cardiac NNCS was followed by the downregulation of GLUT-4 in the db/db mouse heart. Db/db-ChAT-tg mice exhibited preserved cardiac and vascular function in comparison to db/db mice. The improved function was associated with increased cardiac ACh and glucose content, sustained angiogenesis and reduced fibrosis. These beneficial effects were associated with upregulation of the PI3K/Akt/HIF1α signaling pathway, and increased expression of its downstream targets-GLUT-4 and VEGF-A.

conclusionWe provide the first evidence for dysregulation of the cardiac NNCS in DHD. Increased cardiac ACh is beneficial and a potential new therapeutic strategy to prevent or delay the development of DHD.

Indexed as

AcetylcholineAcetylcholinesteraseAgedAnimalsCase-Control StudiesCholine O-AcetyltransferaseDiabetes Mellitus, Type 2Diabetic CardiomyopathiesDisease Models, AnimalFemaleGlucoseGlucose Transporter Type 4GPI-Linked ProteinsHeart VentriclesHumansMaleAcetylcholineAcetylcholinesteraseACHE protein, humanAche protein, mouseCholine O-AcetyltransferaseCHRM2 protein, humanCHT1 protein, mouseGlucoseGlucose Transporter Type 4GPI-Linked ProteinsMembrane Transport ProteinsReceptor, Muscarinic M2SLC18A3 protein, humanSlc18a3 protein, mouseSLC2A4 protein, humanSlc2a4 protein, mouseSLC5A7 protein, humanSymportersVesicular Acetylcholine Transport ProteinsAcetylcholineAngiogenesisDiabetic heart diseaseGlucose metabolismNon-neuronal cholinergic system

Identifiers

PMID33618724
PMCPMC7898760
OpenAlexW3131539792

What OpenQuestion holds

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LicenceCC BY
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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.