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Record W4376134916 · doi:10.1016/j.celrep.2023.112500

Vitamin K-dependent carboxylation regulates Ca2+ flux and adaptation to metabolic stress in β cells

2023· article· en· W4376134916 on OpenAlex
Julie Lacombe, Kevin Guo, Jessica Bonneau, Denis Faubert, Florian Gioanni, Alexis Vivoli, Sarah M. Muir, Soraya Hezzaz, Vincent Poitout, Mathieu Ferron

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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueCell Reports · 2023
Typearticle
Languageen
FieldNursing
TopicVitamin K Research Studies
Canadian institutionsCentre Hospitalier de l’Université de MontréalMcGill UniversityUniversité de MontréalMontreal Clinical Research Institute
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchNational Institute of Diabetes and Digestive and Kidney DiseasesInstitut de Recherche Clinique De MontréalCanada Research ChairsUniversity of AlbertaNational Institutes of HealthDiabetes CanadaDiabète Québec
KeywordsEndoplasmic reticulumUnfolded protein responseCell biologySecretionCarboxylationChemistryFlux (metallurgy)Context (archaeology)ProteostasisPyruvate carboxylaseVitaminBiologyBiochemistryEnzyme

Abstract

fetched live from OpenAlex

Vitamin K is a micronutrient necessary for γ-carboxylation of glutamic acids. This post-translational modification occurs in the endoplasmic reticulum (ER) and affects secreted proteins. Recent clinical studies implicate vitamin K in the pathophysiology of diabetes, but the underlying molecular mechanism remains unknown. Here, we show that mouse β cells lacking γ-carboxylation fail to adapt their insulin secretion in the context of age-related insulin resistance or diet-induced β cell stress. In human islets, γ-carboxylase expression positively correlates with improved insulin secretion in response to glucose. We identify endoplasmic reticulum Gla protein (ERGP) as a γ-carboxylated ER-resident Ca 2+ -binding protein expressed in β cells. Mechanistically, γ-carboxylation of ERGP protects cells against Ca 2+ overfilling by diminishing STIM1 and Orai1 interaction and restraining store-operated Ca 2+ entry. These results reveal a critical role of vitamin K-dependent carboxylation in regulation of Ca 2+ flux in β cells and in their capacity to adapt to metabolic stress.

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)0.001
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 score0.132
Threshold uncertainty score0.639

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
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 head0.022
GPT teacher head0.279
Teacher spread0.257 · 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