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Record W4411156768 · doi:10.1101/2025.06.04.657914

Alpha cell inflammation during human pancreas aging and type 2 diabetes and its reversal by calorie restriction in mice

2025· preprint· en· W4411156768 on OpenAlexaff
Michael W. Schleh, Amanda Cambraia, Melanie Cutler

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsUniversity of Alberta
FundersNational Cancer InstituteNational Institutes of HealthVanderbilt UniversityUniversity of PennsylvaniaVanderbilt University Medical CenterHuman Islet Research NetworkNational Center for Research ResourcesAmerican Heart Association
KeywordsImmune systemBiologyT cellCD8Cytotoxic T cellBeta cellCell biologyProinflammatory cytokineMajor histocompatibility complexEndocrinologyInternal medicineImmunologyInsulinIsletInflammationMedicineIn vitro

Abstract

fetched live from OpenAlex

Abstract Aging increases risk for type 2 diabetes (T2D), partly through loss of beta cell identity and function driven by metabolic stress and islet inflammation. While calorie restriction (CR) promotes beta cell longevity in young animals, its impact on cellular aging and inflammatory burden in older individuals is unclear. Using SCENIC regulon and multiomic analyses, we find that aging human alpha cells adopt a coordinated inflammatory phenotype marked by IFN-γ signaling to increase major histocompatibility complex (MHC) class I presentation, and CD8 + T cell recruitment and activation towards islets. In T2D, CD8 + T cells further progress towards an effector memory state. CR reduces alpha cell MHC-I expression while subsequently suppressing CD8 + effector status and accompanied by reduced islet inflammation and immune cell infiltration in mice. Together, these findings highlight an alpha cell–immune signaling axis in aging and T2D that may underlie fibrosis and disease pathophysiology.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.009
GPT teacher head0.217
Teacher spread0.208 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2025
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicPancreatic function and diabetes→French-language works237,207→