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Record W4376959054 · doi:10.1016/j.celrep.2023.112529

Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells

2023· article· en· W4376959054 on OpenAlexfundno aff
Weiwei Xu, Mirza Muhammad Fahd Qadir, Daniela Nasteska, Paula Mota de, Caroline M. Gorvin, Manuel Blandino-Rosano, Charles R. Evans, Thuong Ho, Evgeniy Potapenko, Rajakrishnan Veluthakal, Fiona Ashford, Stavroula Bitsi, Jia Fan, Manika Bhondeley, Kejing Song, Venkata N. Sure, Siva S. V. P. Sakamuri, Lina Schiffer, Wandy L. Beatty, Rachael A. Wyatt, Daniel E. Frigo, Xiaowen Liu, Prasad V. G. Katakam, Wiebke Arlt, Jochen Buck, Lonny R. Levin, Ye Hu, Jay K. Kolls, Charles Burant, Alejandra Tomás, Matthew J. Merrins, Debbie C. Thurmond, Ernesto Bernal‐Mizrachi, David J. Hodson, Franck Mauvais‐Jarvis

Bibliographic record

VenueCell Reports · 2023
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsnot available
FundersMedical Research CouncilNational Institutes of HealthUniversity of BirminghamEuropean CommissionBirmingham Biomedical Research CentreEngineering and Physical Sciences Research CouncilEli Lilly and CompanyNIHR Bristol Biomedical Research CentreComputer Modelling GroupUniversity Hospitals Birmingham NHS Foundation TrustAcademy of Medical SciencesDepartment for Business, Energy and Industrial Strategy, UK GovernmentBritish Heart FoundationWellcome TrustNational Institute of Diabetes and Digestive and Kidney DiseasesA. Alfred Taubman Medical Research InstituteDiabetes UKNational Institute for Health and Care ResearchMemphis Research ConsortiumU.S. Department of Veterans Affairs
KeywordsGlucagon-like peptide-1Androgen receptorInternal medicineEndocrinologyReceptorAction (physics)AndrogenTestosterone (patch)BiologyChemistryCell biologyHormoneMedicineDiabetes mellitusProstate cancerCancerType 2 diabetes

Abstract

fetched live from OpenAlex

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO 2 , activating the HCO 3 − -sensitive soluble adenylate cyclase; and (2) increased Gα s recruitment to GLP-1 receptor and AR complexes, activating transmembrane adenylate cyclase. Additionally, testosterone enhances GSIS in human islets via a focal adhesion kinase/SRC/phosphatidylinositol 3-kinase/mammalian target of rapamycin complex 2 actin remodeling cascade. We describe the testosterone-stimulated AR interactome, transcriptome, proteome, and metabolome that contribute to these effects. This study identifies AR genomic and non-genomic actions that enhance GLP-1-stimulated insulin exocytosis in male β cells.

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 score0.060
Threshold uncertainty score0.625

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
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 head0.029
GPT teacher head0.252
Teacher spread0.223 · 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

Citations36
Published2023
Admission routes1
Has abstractyes

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