Evidence map›Paper›PMID 19352619›Full record

ArticleDiabetologia2009

Amyloid formation in human IAPP transgenic mouse islets and pancreas, and human pancreas, is not associated with endoplasmic reticulum stress.

R L Hull, S Zraika, J Udayasankar, K Aston-Mourney, S L Subramanian, S E Kahn

Open access · bronzeAbstract read
In one paragraph

Article in Diabetologia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.9field-weighted citation impact, top 10% 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

38 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
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  8. Review
  9. RNA-seq-based identification of Star upregulation by islet amyloid formation.Protein engineering, design & selection : PEDS · 2019
    Article
  10. Review
  11. Article
  12. Amyloid-induced β-cell dysfunction and islet inflammation are ameliorated by 4-phenylbutyrate (PBA) treatment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
    Article
  13. Article
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  15. Article
  16. Review
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  19. Review
  20. Stress and the inflammatory process: a major cause of pancreatic cell death in type 2 diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2014
    Review
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

6 authors at 2 institutions in 1 country.

R L HullDivision of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System (151), Seattle, WA 98108, USA. rhull@u.washington.edu
S Zraika
J Udayasankar
K Aston-Mourney
S L Subramanian
S E Kahn
VA Puget Sound Health Care System · USUniversity of Washington · US

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Sakeneh Zraika · 1986 to 2026
$41.4M
Diabetes, Obesity and Metabolism Training ProgramT32DK007247 · NIDDK · UNIVERSITY OF WASHINGTON · PI GREGORY J MORTON, KRISTINA Marie UTZSCHNEIDER · 1986 to 2026
$10.0M
Mechanisms of Islet AmyloidogenesisR01DK075998 · NIDDK · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · PI KAHN, STEVEN EMANUEL · 2008 to 2011
$1.2M
Role of perlecan in islet amyloid formationK01DK074404 · NIDDK · UNIVERSITY OF WASHINGTON · PI HULL-MEICHLE, REBECCA LUCY · 2006 to 2010
$596k
The role of neprilysin in pancreatic beta-cell dysfunction and deathK99DK080945 · NIDDK · UNIVERSITY OF WASHINGTON · PI ZRAIKA, SAKENEH · 2009 to 2010
$180k
NIDDK NIH HHS DK07247NIDDK NIH HHS DK17047NIDDK NIH HHS DK74404NIDDK NIH HHS DK75998NIDDK NIH HHS K01 DK074404NIDDK NIH HHS K99 DK080945NIDDK NIH HHS P30 DK017047NIDDK NIH HHS R01 DK075998NIDDK NIH HHS T32 DK007247
6 · The paper itself

Abstract

aims/hypothesisSupraphysiological levels of the amyloidogenic peptide human islet amyloid polypeptide have been associated with beta cell endoplasmic reticulum (ER) stress. However, in human type 2 diabetes, levels of human IAPP are equivalent or decreased relative to matched controls. Thus, we sought to investigate whether ER stress is induced during amyloidogenesis at physiological levels of human IAPP.

methodsIslets from human IAPP transgenic mice that develop amyloid, and non-transgenic mice that do not, were cultured for up to 7 days in 11.1, 16.7 and 33.3 mmol/l glucose. Pancreases from human IAPP transgenic and non-transgenic mice and humans with or without type 2 diabetes were also evaluated. Amyloid formation was determined histologically. ER stress was determined in islets by quantifying mRNA levels of Bip, Atf4 and Chop (also known as Ddit3) and alternate splicing of Xbp1 mRNA, or in pancreases by immunostaining for immunoglobulin heavy chain-binding protein (BIP), C/EBP homologous protein (CHOP) and X-box binding protein 1 (XBP1).

resultsAmyloid formation in human IAPP transgenic islets was associated with reduced beta cell area in a glucose- and time-dependent manner. However, amyloid formation was not associated with significant increases in expression of ER stress markers under any culture condition. Thapsigargin treatment, a positive control, did result in significant ER stress. Amyloid formation in vivo in pancreas samples from human IAPP transgenic mice or humans was not associated with upregulation of ER stress markers. CONCLUSIONS/

interpretationOur data suggest that ER stress is not an obligatory pathway mediating the toxic effects of amyloid formation at physiological levels of human IAPP.

Indexed as

AmyloidAnimalsDNA-Binding ProteinsElectrophoresis, Agar GelEndoplasmic ReticulumFemaleGlucoseHumansImmunohistochemistryIslet Amyloid PolypeptideIslets of LangerhansMaleMiceMice, TransgenicOrgan Culture TechniquesPancreasAmyloidDNA-Binding ProteinsGlucoseIslet Amyloid PolypeptideRegulatory Factor X Transcription FactorsTranscription FactorsX-Box Binding Protein 1XBP1 protein, humanXbp1 protein, mouse

Identifiers

PMID19352619
PMCPMC2734275
OpenAlexW2033484052

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.