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Record W3024724815 · doi:10.1016/j.celrep.2020.107761

Vitamin-D-Binding Protein Contributes to the Maintenance of α Cell Function and Glucagon Secretion

2020· article· en· W3024724815 on OpenAlexafffund
Katrina Viloria, Daniela Nasteska, Linford J.B. Briant, Silke Heising, Dean P. Larner, Nicholas H. F. Fine, Fiona Ashford, Gabriela da Silva Xavier, Maria Jiménez Ramos, Annie Hasib, Federica Cuozzo, Jocelyn E. Manning Fox, Patrick E. MacDonald, İldem Akerman, Gareth G. Lavery, Christine S. Flaxman, Noel G. Morgan, Sarah J. Richardson, Martin Hewison, David J. Hodson

Bibliographic record

VenueCell Reports · 2020
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsUniversity of Alberta
FundersEuropean Research CouncilMedical Research CouncilCanadian Institutes of Health ResearchEuropean CommissionDiabetes UKUniversity of AlbertaWellcome TrustJuvenile Diabetes Research Foundation United Kingdom
KeywordsSecretionVitamin D and neurologyFunction (biology)Vitamin D-binding proteinGlucagonChemistryEndocrinologyCell biologyInternal medicineBiologyBiochemistryHormoneMedicine

Abstract

fetched live from OpenAlex

Vitamin-D-binding protein (DBP) or group-specific component of serum (GC-globulin) carries vitamin D metabolites from the circulation to target tissues. DBP is highly localized to the liver and pancreatic α cells. Although DBP serum levels, gene polymorphisms, and autoantigens have all been associated with diabetes risk, the underlying mechanisms remain unknown. Here, we show that DBP regulates α cell morphology, α cell function, and glucagon secretion. Deletion of DBP leads to smaller and hyperplastic α cells, altered Na+ channel conductance, impaired α cell activation by low glucose, and reduced rates of glucagon secretion both in vivo and in vitro. Mechanistically, this involves reversible changes in islet microfilament abundance and density, as well as changes in glucagon granule distribution. Defects are also seen in β cell and δ cell function. Immunostaining of human pancreata reveals generalized loss of DBP expression as a feature of late-onset and long-standing, but not early-onset, type 1 diabetes. Thus, DBP regulates α cell phenotype, with implications for diabetes pathogenesis.

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 score0.022
Threshold uncertainty score0.250

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 head0.010
GPT teacher head0.209
Teacher spread0.199 · 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

Citations38
Published2020
Admission routes2
Has abstractyes

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