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Record W4394722806 · doi:10.1016/j.celrep.2024.114047

LDHB contributes to the regulation of lactate levels and basal insulin secretion in human pancreatic β cells

2024· article· en· W4394722806 on OpenAlexafffund
Federica Cuozzo, Katrina Viloria, Ali H. Shilleh, Daniela Nasteska, Charlotte Frazer-Morris, Jason Tong, Zicong Jiao, Adam Boufersaoui, Bryan P. Marzullo, Daniel B. Rosoff, Hannah Smith, Caroline Bonner, J. Kerr–Conte, François Pattou, Rita Nano, Lorenzo Piemonti, Paul Johnson, Rebecca Spiers, Jennie Roberts, Gareth G. Lavery, Anne Clark, Carlo Ceresa, David Ray, Leanne Hodson, A. Davies, Guy A. Rutter, Masaya Oshima, Raphaël Scharfmann, Matthew J. Merrins, İldem Akerman, Daniel A. Tennant, Christian Ludwig, David J. Hodson

Bibliographic record

VenueCell Reports · 2024
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsUniversité de Montréal
FundersCancer Research UK Cambridge Institute, University of CambridgeNIHR Oxford Biomedical Research CentreHorizon 2020European Research CouncilWellcome TrustCancer Research UKBiotechnology and Biological Sciences Research CouncilMedical Research CouncilDiabetes UKJuvenile Diabetes Research Foundation United KingdomCanadian Institutes of Health ResearchSusan McKinnon FoundationStichting Diabetes Onderzoek NederlandDiabetes FondsUniversity of AlbertaEuropean CommissionHorizon 2020 Framework ProgrammeAcademy of Medical SciencesDiabetes Research and Wellness FoundationNovo NordiskNational Institute for Health and Care ResearchU.S. Department of Veterans AffairsNational Institutes of HealthNational Institute of Diabetes and Digestive and Kidney DiseasesNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchEngineering and Physical Sciences Research CouncilUK Research and InnovationBritish Heart Foundation
KeywordsSecretionBasal (medicine)EndocrinologyInternal medicineInsulinBiologyChemistryCell biologyMedicine

Abstract

fetched live from OpenAlex

C heteronuclear single quantum coherence NMR spectroscopy, we have obtained a comparative high-resolution map of glucose fate underpinning β cell function. In both mouse and human islets, the contribution of glucose to the tricarboxylic acid (TCA) cycle is similar. Pyruvate fueling of the TCA cycle is primarily mediated by the activity of pyruvate dehydrogenase, with lower flux through pyruvate carboxylase. While the conversion of pyruvate to lactate by lactate dehydrogenase (LDH) can be detected in islets of both species, lactate accumulation is 6-fold higher in human islets. Human islets express LDH, with low-moderate LDHA expression and β cell-specific LDHB expression. LDHB inhibition amplifies LDHA-dependent lactate generation in mouse and human β cells and increases basal insulin release. Lastly, cis-instrument Mendelian randomization shows that low LDHB expression levels correlate with elevated fasting insulin in humans. Thus, LDHB limits lactate generation in β cells to maintain appropriate insulin release.

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.

How this classification was reachedexpand

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 score0.416
Threshold uncertainty score0.241

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)0.0000.000

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 head0.015
GPT teacher head0.254
Teacher spread0.239 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations25
Published2024
Admission routes2
Has abstractyes

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