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Record W4409910964 · doi:10.1021/jacs.4c15698

Faster Amylin Aggregation on Fibrillar Collagen I Hastens Diabetic Progression through β-Cell Death and Loss of Function

2025· article· en· W4409910964 on OpenAlexaff
Md Asrafuddoza Hazari, Gautam Kannan, Subrata Dasgupta, Musale Krushna Pavan, Akash Kumar Jha, Farhin Sultana, Soumya Ranjan Pujahari, Simran Singh, Sarbajeet Dutta, Sai P. Pydi, Sankhadeep Dutta, Hamim Zafar, Prasenjit Bhaumik, Ashutosh Kumar, Shamik Sen

Bibliographic record

VenueJournal of the American Chemical Society · 2025
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsCentre for Family Medicine
FundersCouncil of Scientific and Industrial Research, IndiaDepartment of Biotechnology, Ministry of Science and Technology, IndiaUniversity Grants CommissionWadhwani Research Centre for Bioengineering, Indian Institute of Technology Bombay
KeywordsAmylinIsletChemistryExtracellular matrixAmyloid (mycology)Programmed cell deathCell biologyPeptideExtracellularSecretionApoptosisInternal medicineDiabetes mellitusEndocrinologyBiochemistryBiologyMedicine

Abstract

fetched live from OpenAlex

Amyloid deposition of the neuroendocrine peptide amylin in islet tissues is a hallmark of type 2 diabetes (T2DM), leading to β-cell toxicity through nutrient deprivation, membrane rupture, and apoptosis. Though accumulation of toxic amylin aggregates in islet matrices is well documented, the role of the islet extracellular matrix in mediating amylin aggregation and its pathological consequences remains elusive. Here, we address this question by probing amylin interaction with collagen I (Col)─whose expression in the islet tissue increases during diabetes progression. By combining multiple biophysical techniques, we show that hydrophobic, hydrophilic, and cation-π interactions regulate amylin binding to Col, with fibrillar Col driving faster amylin aggregation. Amylin-entangled Col matrices containing high amounts of amylin induce death and loss of function in INS1E β-cells. Together, our results illustrate how amylin incorporation in islet matrices through amylin-Col interactions drives T2DM progression by impacting β-cell viability and insulin secretion.

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 score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

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

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 head0.011
GPT teacher head0.270
Teacher spread0.259 · 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

Citations5
Published2025
Admission routes1
Has abstractyes

Explore more

Same venueJournal of the American Chemical Society→Same topicPancreatic function and diabetes→French-language works237,207→