Evidence mapPaperPMID 40757436Full record

ArticleDiabetes, obesity & metabolism2025

Loss of β-cell identity in human islets treated with glibenclamide.

Claudia Fernández, Montserrat Nacher, Kevin Rivera, Sandra Marín-Cañas, Maria Sorribas, Gabriel Moreno-González, Elisabet Estil Les, Patricia San José, Noèlia Téllez, Eduard Montanya

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Article in Diabetes, obesity & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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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

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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

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Claudia FernándezDepartment of Clinical Sciences, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
Montserrat NacherBellvitge Biomedical Research Institute, (IDIBELL).
Kevin RiveraDepartment of Clinical Sciences, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
Sandra Marín-CañasBellvitge Biomedical Research Institute, (IDIBELL).
Maria SorribasHospital Universitari de Bellvitge.
Gabriel Moreno-GonzálezBellvitge Biomedical Research Institute, (IDIBELL).
Elisabet Estil LesBellvitge Biomedical Research Institute, (IDIBELL).
Patricia San JoséBellvitge Biomedical Research Institute, (IDIBELL).
Noèlia TéllezBellvitge Biomedical Research Institute, (IDIBELL).
Eduard MontanyaDepartment of Clinical Sciences, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.ORCID https://orcid.org/0000-0003-2518-9076

Funding

Agència de Gestió d'Ajuts Universitaris i de RecercaCampus Ciències de la Salut de Bellvitge, Universitat de Barcelona, APIFCentro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas AsociadasEuropean Regional Development FundInstituto de Salud Carlos III (Spain) PI19/00246Instituto de Salud Carlos III (Spain) PI22/00334
6 · The paper itself

Abstract

aimsLoss of β-cell identity can contribute to the reduction of functional β-cell mass in type 2 diabetes. Sulfonylureas show shorter durability of antihyperglycaemic action and higher rates of secondary failure compared to other antihyperglycaemic agents, suggesting that they could accelerate the decline of β-cell functional mass in type 2 diabetes. We aimed to investigate the impact of chronic exposure to sulfonylureas on β-cell identity. MATERIALS AND

methodsIslets from human multi-organ donors were cultured for 4-7 days at 5.6 mM glucose with or without glibenclamide. β-cell function (glucose stimulated insulin secretion, GSIS), apoptosis (TUNEL) and gene (RT-qPCR) and protein expression (immunofluorescence, genetic β-cell tracing and Western Blot) were determined.

resultsHuman islets exposed to glibenclamide showed increased insulin secretion at low glucose, reduced GSIS, increased apoptosis, endoplasmic reticulum (ER) stress, and loss of β-cell identity indicated by reduced gene and protein expression of key β-cell identity markers and insulin. There were no changes in the expression of disallowed or progenitor-related genes. Genetic β-cell tracing showed a similar percentage of insulin-expressing cells in control and sulfonylurea-treated islets. Addition of the chemical chaperone 4-phenylbutyrate (PBA) to the culture medium prevented glibenclamide-induced ER stress and the downregulation of key β-cell transcription factors, indicating that ER stress mediates, at least partially, the negative effects of glibenclamide on β-cell identity.

conclusionsChronic exposure of human islets to glibenclamide induced the loss of β-cell identity, which was mediated by ER stress, impaired β-cell function, and increased β-cell apoptosis. These negative effects of glibenclamide may contribute to the secondary failure of sulfonylureas and accelerate the decline of functional β-cell mass in patients with type 2 diabetes.

Indexed as

Diabetes Mellitus, Type 2GlyburideHypoglycemic AgentsInsulin-Secreting CellsIslets of LangerhansAdultApoptosisCells, CulturedEndoplasmic Reticulum StressFemaleGlucoseHumansInsulinInsulin SecretionMaleMiddle AgedGlucoseGlyburideHypoglycemic AgentsInsulinantidiabetic drugbeta cell functionisletssulphonylureastype 2 diabetes

Identifiers

PMID40757436
PMCPMC12409205

What Socratic holds

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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.