Evidence map›Paper›PMID 34554282›Full record

ArticleDiabetologia2022

IAPP-induced beta cell stress recapitulates the islet transcriptome in type 2 diabetes.

Montgomery Blencowe, Allison Furterer, Qing Wang, Fuying Gao, Madeline Rosenberger, Lina Pei, Hiroshi Nomoto, Alex M Mawla, Mark O Huising, Giovanni Coppola and 3 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetologia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
9.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
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  12. Investigation of Pancreatic-beta Cells Role in the Biological Process of Ageing.Endocrine, metabolic & immune disorders drug targets · 2024
    Review
  13. Impact of CaBiochimica et biophysica acta. Biomembranes · 2023
    Article
  14. Review
  15. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Montgomery BlencoweDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Allison FurtererSemel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
Qing WangSemel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
Fuying GaoSemel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
Madeline RosenbergerLarry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
Lina PeiLarry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
Hiroshi NomotoLarry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
Alex M MawlaDepartment of Neurobiology, Physiology and Behavior, College of Biological Sciences, University of California, Davis, Davis, CA, USA.
Mark O HuisingDepartment of Neurobiology, Physiology and Behavior, College of Biological Sciences, University of California, Davis, Davis, CA, USA.
Giovanni CoppolaSemel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
Xia YangDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Peter C ButlerLarry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
Tatyana GurloLarry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA. tgurlo@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of California, Davis · US

Funding

Role of IAPP in Islet Dysfunction in DiabetesR01DK059579 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUTLER, PETER CAWOOD · 2001 to 2019
$7.5M
Integrative Center for Neurogenetics and Neurogenomics - OverallP30NS062691 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ESKIN, ELEAZAR · 2009 to 2018
$7.4M
NIDDK NIH HHS R01 DK059579NINDS NIH HHS P30 NS062691
6 · The paper itself

Abstract

aims/hypothesisType 2 diabetes is characterised by islet amyloid and toxic oligomers of islet amyloid polypeptide (IAPP). We posed the questions, (1) does IAPP toxicity induce an islet response comparable to that in humans with type 2 diabetes, and if so, (2) what are the key transcriptional drivers of this response?

methodsThe islet transcriptome was evaluated in five groups of mice: beta cell specific transgenic for (1) human IAPP, (2) rodent IAPP, (3) human calpastatin, (4) human calpastatin and human IAPP, and (5) wild-type mice. RNA sequencing data was analysed by differential expression analysis and gene co-expression network analysis to establish the islet response to adaptation to an increased beta cell workload of soluble rodent IAPP, the islet response to increased expression of oligomeric human IAPP, and the extent to which the latter was rescued by suppression of calpain hyperactivation by calpastatin. Rank-rank hypergeometric overlap analysis was used to compare the transcriptome of islets from human or rodent IAPP transgenic mice vs humans with prediabetes or type 2 diabetes.

resultsThe islet transcriptomes in humans with prediabetes and type 2 diabetes are remarkably similar. Beta cell overexpression of soluble rodent or oligomer-prone human IAPP induced changes in islet transcriptome present in prediabetes and type 2 diabetes, including decreased expression of genes that confer beta cell identity. Increased expression of human IAPP, but not rodent IAPP, induced islet inflammation present in prediabetes and type 2 diabetes in humans. Key mediators of the injury responses in islets transgenic for human IAPP or those from individuals with type 2 diabetes include STAT3, NF-κB, ESR1 and CTNNB1 by transcription factor analysis and COL3A1, NID1 and ZNF800 by gene regulatory network analysis. CONCLUSIONS/

interpretationBeta cell injury mediated by IAPP is a plausible mechanism to contribute to islet inflammation and dedifferentiation in type 2 diabetes. Inhibition of IAPP toxicity is a potential therapeutic target in type 2 diabetes.

Indexed as

Diabetes Mellitus, Type 2Insulin-Secreting CellsIslets of LangerhansAmyloidAnimalsIslet Amyloid PolypeptideMiceMice, TransgenicTranscriptomeAmyloidIslet Amyloid PolypeptideBeta cellCell cycleDedifferentiationInflammationIslet amyloid polypeptidePrediabetesProtein misfoldingType 2 diabetesUnfolded protein response

Identifiers

PMID34554282
PMCPMC8660728
OpenAlexW3201026687

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.