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Record W3109862518 · doi:10.1016/j.celrep.2020.108466

Persistent or Transient Human β Cell Dysfunction Induced by Metabolic Stress: Specific Signatures and Shared Gene Expression with Type 2 Diabetes

2020· article· en· W3109862518 on OpenAlex
Lorella Marselli, Anthony Piron, Mara Suleiman, Máikel L. Colli, Xiaoyan Yi, Amna Khamis, Gaëlle Carrat, Guy A. Rutter, Marco Bugliani, Laura Giusti, Maurizio Ronci, Mark Ibberson, Jean‐Valéry Turatsinze, Ugo Boggi, Paolo De Simone, Vincenzo De Tata, Miguel Lopes, Daniela Nasteska, Carmela De Luca, Marta Tesi, Emanuele Bosi, Pratibha Singh, Daniela Campani, Anke M. Schulte, Michele Solimena, Peter Hecht, Brian Rady, Ivona Bakaj, Alessandro Pocai, Lisa Norquay, Bernard Thorens, Mickaël Canouil, Philippe Froguel, Décio L. Eizirik, Miriam Cnop, Piero Marchetti

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueCell Reports · 2020
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsnot available
FundersHorizon 2020Medical Research CouncilCentre National de la Recherche ScientifiqueULB Center for Diabetes ResearchFonds De La Recherche Scientifique - FNRSSingapore Eye Research InstituteEuropean CommissionInstitut national de la recherche scientifiqueWellcome TrustAgence Nationale de la RechercheJuvenile Diabetes Research Foundation United States of AmericaHorizon 2020 Framework ProgrammeLeona M. and Harry B. Helmsley Charitable TrustJanssen Research and DevelopmentSociété Francophone du DiabèteInnovirisEquipexEuropean Federation of Pharmaceutical Industries and AssociationsInnovative Medicines InitiativeWellcome
KeywordsIsletTranscriptomeBiologyType 2 diabetesGene expressionGeneCell typeCellCell biologyInsulinDiabetes mellitusGeneticsEndocrinology

Abstract

fetched live from OpenAlex

Pancreatic β cell failure is key to type 2 diabetes (T2D) onset and progression. Here, we assess whether human β cell dysfunction induced by metabolic stress is reversible, evaluate the molecular pathways underlying persistent or transient damage, and explore the relationships with T2D islet traits. Twenty-six islet preparations are exposed to several lipotoxic/glucotoxic conditions, some of which impair insulin release, depending on stressor type, concentration, and combination. The reversal of dysfunction occurs after washout for some, although not all, of the lipoglucotoxic insults. Islet transcriptomes assessed by RNA sequencing and expression quantitative trait loci (eQTL) analysis identify specific pathways underlying β cell failure and recovery. Comparison of a large number of human T2D islet transcriptomes with those of persistent or reversible β cell lipoglucotoxicity show shared gene expression signatures. The identification of mechanisms associated with human β cell dysfunction and recovery and their overlap with T2D islet traits provide insights into T2D pathogenesis, fostering the development of improved β cell-targeted therapeutic strategies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.760

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.220
Teacher spread0.197 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it