MétaCan
Menu
Back to cohort
Record W4282821612 · doi:10.1016/j.isci.2022.104603

Uncoupling protein 2 and aldolase B impact insulin release by modulating mitochondrial function and Ca2+ release from the ER

2022· article· en· W4282821612 on OpenAlexafffund
Ryota Inoue, Takahiro Tsuno, Yu Togashi, Tomoko Okuyama, Aoi Sato, Kuniyuki Nishiyama, Mayu Kyohara, Jinghe Li, Setsuko Fukushima, Tatsuya Kin, Daisuke Miyashita, Yusuke Shiba, Yoshitoshi Atobe, Hiroshi Kiyonari, Kana Bando, A. M. James Shapiro, Kengo Funakoshi, Rohit Kulkarni, Yasuo Terauchi, Jun Shirakawa

Bibliographic record

VenueiScience · 2022
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsUniversity of Alberta
FundersJapan Science and Technology AgencyNational Institutes of HealthJapan Diabetes FoundationNational Institute of Diabetes and Digestive and Kidney DiseasesAstellas Foundation for Research on Metabolic DisordersGunma UniversityMochida Memorial Foundation for Medical and Pharmaceutical ResearchYokohama City UniversityJapan IDDM networkMinistry of Education, Culture, Sports, Science and TechnologyUniversity of AlbertaKobe UniversityJapan Agency for Medical Research and DevelopmentUehara Memorial FoundationNaito Foundation
KeywordsEndoplasmic reticulumUnfolded protein responseMitochondrionInternal medicineDownregulation and upregulationEndocrinologyGlycolysisPancreatic isletsSecretionInsulinCell biologyOxidative stressTransgeneGenetically modified mouseBiologyIsletChemistryBiochemistryMetabolismMedicineGene

Abstract

fetched live from OpenAlex

Uncoupling protein 2 (UCP2), a mitochondrial protein, is known to be upregulated in pancreatic islets of patients with type 2 diabetes (T2DM); however, the pathological significance of this increase in UCP2 expression is unclear. In this study, we highlight the molecular link between the increase in UCP2 expression in β-cells and β-cell failure by using genetically engineered mice and human islets. β-cell-specific UCP2-overexpressing transgenic mice (βUCP2Tg) exhibited glucose intolerance and a reduction in insulin secretion. Decreased mitochondrial function and increased aldolase B (AldB) expression through oxidative-stress-mediated pathway were observed in βUCP2Tg islets. AldB, a glycolytic enzyme, was associated with reduced insulin secretion via mitochondrial dysfunction and impaired calcium release from the endoplasmic reticulum (ER). Taken together, our findings provide a new mechanism of β-cell dysfunction by UCP2 and AldB. Targeting the UCP2/AldB axis is a promising approach for the recovery of β-cell function.

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)0.001
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 score0.893
Threshold uncertainty score0.400

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
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 head0.012
GPT teacher head0.243
Teacher spread0.231 · 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

Citations18
Published2022
Admission routes2
Has abstractyes

Explore more

Same venueiScienceSame topicPancreatic function and diabetesFrench-language works237,207