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Record W2151867562

Role of methylglyoxal in the pathogenesis of insulin resistance

2010· article· en· W2151867562 on OpenAlexfundno aff
Xuming Jia

Bibliographic record

VenueUniversity Library - University of Saskatchewan (University of Saskatchewan) · 2010
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAdvanced Glycation End Products research
Canadian institutionsnot available
FundersHeart and Stroke Foundation of Canada
KeywordsInsulinInternal medicineEndocrinologyMethylglyoxalInsulin resistanceInsulin receptorChemistryPathogenesisGlucose uptakeDiabetes mellitusBiologyBiochemistryMedicineEnzyme
DOInot available

Abstract

fetched live from OpenAlex

Methylglyoxal (MG) is a reactive metabolite presents in all biological systems.The accumulation of MG in diabetic patients and animals has been long recognized.Recently, studies have shown that MG levels are elevated in hypertensive rats.However, the pathological effects of MG in diabetes and related insulin resistance syndrome such as obesity are currently unknown.In the present study, the role of MG in the pathogenesis of insulin resistance was investigated.First, it was observed that MG induced structural and functional changes of insulin.Incubation of human insulin with MG in vitro yielded MG-insulin adducts, as evidenced by additional peaks observed upon mass spectrometric (MS) analysis.Tandem MS analysis of insulin B-chain adducts confirmed attachment of MG at an arginine residue.[ 3 H]-2-deoxyglucose uptake ([ 3 H]-2-DOG) by 3T3-L1 adipocytes was significantly and concentration-dependently decreased after treatment with MG-insulin adducts, in comparison with the effect of native insulin at the same concentration.A significant decrease of glucose uptake induced by MG-insulin adducts was also observed in L8 skeletal muscle cells.Unlike native insulin, MG-insulin adducts did not inhibit insulin release from pancreatic -cells.The degradation of MG-insulin by cultured liver cells was also decreased.In conclusion, MG modifies insulin by attaching to internal arginine residue in the -chain of insulin.The formation of this MG-insulin adduct decreases insulin-mediated glucose uptake, impairs autocrine control of insulin secretion, and decreases insulin clearance.These structural and functional abnormalities of the insulin molecule may contribute to the pathogenesis of insulin resistance.

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 categoriesMeta-epidemiology (narrow)
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 score0.791
Threshold uncertainty score1.000

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 studies0.0000.001
Scholarly communication0.0000.000
Open science0.0020.001
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 head0.006
GPT teacher head0.189
Teacher spread0.183 · 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.

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

Citations2
Published2010
Admission routes1
Has abstractyes

Explore more

Same venueUniversity Library - University of Saskatchewan (University of Saskatchewan)Same topicAdvanced Glycation End Products researchFrench-language works237,207