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Record W4205149390 · doi:10.1038/s41467-021-27540-w

Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells

2022· article· en· W4205149390 on OpenAlexaff
Jaroslawna Meister, Derek B.J. Bone, Jonas R. Knudsen, Luiz F. Barella, Thomas J. Velenosi, Dmitry Akhmedov, Regina J. Lee, Amanda Cohen, Oksana Gavrilova, Yinghong Cui, Gérard Karsenty, Min Chen, Lee S. Weinstein, Maximilian Kleinert, Rebecca Berdeaux, Thomas E. Jensen, Erik A. Richter, Jürgen Wess

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldAgricultural and Biological Sciences
TopicPharmacological Effects and Assays
Canadian institutionsUniversity of British Columbia
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Cancer InstituteNational Institutes of HealthLundbeckfondenNovo Nordisk FondenUniversité de StrasbourgNational Institute on AgingUniversität Basel
KeywordsClenbuterolSkeletal muscleReprogrammingEndocrinologyMedicineInternal medicinePharmacologyCell biologyChemistryBiologyBiochemistryCell

Abstract

fetched live from OpenAlex

Abstract Activation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with β 2- adrenergic receptor agonists results in multiple beneficial metabolic effects, including improved glucose homeostasis. To elucidate the underlying cellular and molecular mechanisms, we chronically treated wild-type mice and several newly developed mutant mouse strains with clenbuterol, a selective β 2 -adrenergic receptor agonist. Clenbuterol administration caused pronounced improvements in glucose homeostasis and prevented the metabolic deficits in mouse models of β-cell dysfunction and insulin resistance. Studies with skeletal muscle-specific mutant mice demonstrated that these metabolic improvements required activation of skeletal muscle β 2 -adrenergic receptors and the stimulatory G protein, G s . Unbiased transcriptomic and metabolomic analyses showed that chronic β 2 -adrenergic receptor stimulation caused metabolic reprogramming of skeletal muscle characterized by enhanced glucose utilization. These findings strongly suggest that agents targeting skeletal muscle metabolism by modulating β 2 -adrenergic receptor-dependent signaling pathways may prove beneficial as antidiabetic drugs.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.808
Threshold uncertainty score0.503

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 studies0.0010.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
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 head0.028
GPT teacher head0.292
Teacher spread0.264 · 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

Citations27
Published2022
Admission routes1
Has abstractyes

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