Evidence mapPaperPMID 28630491Full record

ArticleScientific reports2017

Chronic high fat feeding restricts islet mRNA translation initiation independently of ER stress via DNA damage and p53 activation.

Masayuki Hatanaka, Emily Anderson-Baucum, Alexander Lakhter, Tatsuyoshi Kono, Bernhard Maier, Sarah A Tersey, Yukio Tanizawa, Carmella Evans-Molina, Raghavendra G Mirmira, Emily K Sims

Abstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
field-weighted citation impact
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

15 citing papers in PubMed.

  1. 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

10 authors.

Masayuki HatanakaDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Emily Anderson-BaucumDepartment of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Alexander LakhterDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Tatsuyoshi KonoDepartment of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Bernhard MaierDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Sarah A TerseyDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Yukio TanizawaDivision of Endocrinology, Metabolism, Hematological Sciences and Therapeutics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
Carmella Evans-MolinaDepartment of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Raghavendra G MirmiraDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Emily K SimsDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA. eksims@iu.edu.ORCID 0000-0002-4393-954X

Funding

Translation CoreP30DK097512 · INDIANA UNIVERSITY INDIANAPOLIS · 2025 to 2025
$1.7M
Transcriptional and Translational Mechanisms Governing Beta Cell FunctionR01DK060581 · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · 2002 to 2025
$1.5M
RESEARCH TRAINING PROGRAM IN DIABETES AND OBESITYT32DK064466 · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · 2003 to 2025
$779k
Regulation of Calcium Homeostasis in the Pancreatic Beta CellI01BX001733 · VA · RLR VA MEDICAL CENTER · 2021 to 2025
BLRD VA I01 BX001733NIDDK NIH HHS F32 DK104501NIDDK NIH HHS K08 DK103983NIDDK NIH HHS P30 DK097512NIDDK NIH HHS R01 DK060581NIDDK NIH HHS R01 DK093954NIDDK NIH HHS T32 DK064466NIDDK NIH HHS UC4 DK104166
6 · The paper itself

Abstract

Under conditions of high fat diet (HFD) consumption, glucose dyshomeostasis develops when β-cells are unable to adapt to peripheral insulin demands. Few studies have interrogated the molecular mechanisms of β-cell dysfunction at the level of mRNA translation under such conditions. We sought to address this issue through polyribosome profile analysis of islets from mice fed 16-weeks of 42% HFD. HFD-islet analysis revealed clear trends toward global reductions in mRNA translation with a significant reduction in the polyribosome/monoribosome ratio for Pdx1 mRNA. Transcriptional and translational analyses revealed endoplasmic reticulum stress was not the etiology of our findings. HFD-islets demonstrated evidence of oxidative stress and DNA damage, as well as activation of p53. Experiments in MIN-6 β-cells revealed that treatment with doxorubicin to directly induce DNA damage mimicked our observed effects in islets. Islets from animals treated with pioglitazone concurrently with HFD demonstrated a reversal of effects observed from HFD alone. Finally, HFD-islets demonstrated reduced expression of multiple ribosome biogenesis genes and the key translation initiation factor eIF4E. We propose a heretofore unappreciated effect of chronic HFD on β-cells, wherein continued DNA damage owing to persistent oxidative stress results in p53 activation and a resultant inhibition of mRNA translation.

Indexed as

DNA DamageAnimalsDietary FatsDoxorubicinEndoplasmic Reticulum StressHomeodomain ProteinsInsulin-Secreting CellsMaleMiceProtein BiosynthesisRNA, MessengerTrans-ActivatorsTumor Suppressor Protein p53Dietary FatsDoxorubicinHomeodomain Proteinspancreatic and duodenal homeobox 1 proteinRNA, MessengerTrans-ActivatorsTrp53 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID28630491
PMCPMC5476640

What Socratic holds

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LicenceCC BY
Read underepoch 390

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 Socratic graph.