Evidence map›Paper›PMID 38747277›Full record

ArticleBioscience reports2024

Co-localization of the sodium-glucose co-transporter-2 channel (SGLT-2) with endothelin ETA and ETB receptors in human cardiorenal tissue.

Thomas L Williams, Rhoda E Kuc, Anna L Paterson, George R Abraham, Anna L Pullinger, Janet J Maguire, Sanjay Sinha, Peter J Greasley, Philip Ambery, Anthony P Davenport

Abstract read
In one paragraph

Article in Bioscience reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

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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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

10 authors.

Thomas L WilliamsDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke's Hospital, Cambridge U.K.
Rhoda E KucDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke's Hospital, Cambridge U.K.
Anna L PatersonDepartment of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, U.K.
George R AbrahamDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke's Hospital, Cambridge U.K.
Anna L PullingerDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke's Hospital, Cambridge U.K.
Janet J MaguireDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke's Hospital, Cambridge U.K.
Sanjay SinhaWellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, U.K.
Peter J GreasleyEarly Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Philip AmberyLate-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Anthony P DavenportDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke's Hospital, Cambridge U.K.ORCID 0000-0002-2096-3117

Funding

British Heart Foundation (BHF) FS/18/46/33663British Heart Foundation (BHF) FS/4yPhD/F/21/34156Medical Research Council MC_PC_17230NIHR BioResource (National Institute for Health Research Bioresource)Wellcome TrustWellcome Trust (WT) 203814/Z/16/A
6 · The paper itself

Abstract

Endothelin (ET) receptor antagonists are being investigated in combination with sodium-glucose co-transporter-2 inhibitors (SGLT-2i). These drugs primarily inhibit the SGLT-2 transporter that, in humans, is thought to be mainly restricted to the renal proximal convoluted tubule, resulting in increased glucose excretion favouring improved glycaemic control and diuresis. This action reduces fluid retention with ET receptor antagonists. Studies have suggested SGLT-2 may also be expressed in cardiomyocytes of human heart. To understand the potential of combining the two classes of drugs, our aim was to compare the distribution of ET receptor sub-types in human kidney, with SGLT-2. Secondly, using the same experimental conditions, we determined if SGLT-2 expression could be detected in human heart and whether the transporter co-localised with ET receptors.

methodsImmunocytochemistry localised SGLT-2, ETA and ETB receptors in sections of histologically normal kidney, left ventricle from patients undergoing heart transplantation or controls. Primary antisera were visualised using fluorescent microscopy. Image analysis was used to measure intensity compared with background in adjacent control sections.

resultsAs expected, SGLT-2 localised to epithelial cells of the proximal convoluted tubules, and co-localised with both ET receptor sub-types. Similarly, ETA receptors predominated in cardiomyocytes; low (compared with kidney but above background) positive staining was also detected for SGLT-2. DISCUSSION: Whether low levels of SGLT-2 have a (patho)physiological role in cardiomyocytes is not known but results suggest the effect of direct blockade of sodium (and glucose) influx via SGLT-2 inhibition in cardiomyocytes should be explored, with potential for additive effects with ETA antagonists.

Indexed as

Receptor, Endothelin AReceptor, Endothelin BSodium-Glucose Transporter 2HumansKidneyKidney Tubules, ProximalMyocardiumSodium-Glucose Transporter 2 InhibitorsReceptor, Endothelin AReceptor, Endothelin BSLC5A2 protein, humanSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsEndothelin-1SGLT-2sodium-glucose co-transporter-2sodium-glucose co-transporter-2 inhibitors

Identifiers

PMID38747277
PMCPMC11147812

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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.