Evidence map›Paper›PMID 28575111›Full record

ArticlePloS one2017

The role of insulin resistance in experimental diabetic retinopathy-Genetic and molecular aspects.

Patrick Järgen, Axel Dietrich, Andreas W Herling, Hans-Peter Hammes, Paulus Wohlfart

Open access · goldAbstract readComparative Study
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 2 pooled it
1.2field-weighted citation impact, top 22% 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

11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
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

5 authors at 2 institutions in 1 country.

Patrick Järgen5th Medical Department, Universitätsmedizin Mannheim (UMM), University of Heidelberg, Mannheim, Germany.
Axel DietrichSanofi Aventis Deutschland GmbH, R&D Lead Generation Candidate Realization, Structure, Design and Informatics, Industriepark Höchst, Frankfurt, Germany.
Andreas W HerlingSanofi Aventis Deutschland GmbH, TA Diabetes R&D, Industriepark Höchst, Frankfurt, Germany.
Hans-Peter Hammes5th Medical Department, Universitätsmedizin Mannheim (UMM), University of Heidelberg, Mannheim, Germany.
Paulus WohlfartSanofi Aventis Deutschland GmbH, TA Diabetes R&D, Industriepark Höchst, Frankfurt, Germany.ORCID http://orcid.org/0000-0002-0986-5911
Sanofi (Germany) · DEHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDiabetic retinopathy is characterized by defects in the retinal neurovascular unit. The underlying mechanisms of impairment-including reactive intermediates and growth-factor dependent signalling pathways and their possible interplay are incompletely understood. This study aims to assess the relative role of hyperglycemia and hyperinsulinemia alone or in combination on the gene expression patterning in the retina of animal models of diabetes. MATERIAL AND

methodsAs insulinopenic, hyperglycemic model reflecting type 1 diabetes, male STZ-Wistar rats (60mg/kg BW; i.p. injection at life age week 7) were used. Male obese ZDF rats (fa/fa) were used as type-2 diabetes model characterized by persisting hyperglycemia and transient hyperinsulinemia. Male obese ZF rats (fa/fa) were used reflecting euglycemia and severe insulin resistance. All groups were kept till an age of 20 weeks on respective conditions together with appropriate age-matched controls. Unbiased gene expression analysis was performed per group using Affymetrix gene arrays. Bioinformatics analysis included analysis for clustering and differential gene expression, and pathway and upstream activator analysis. Gene expression differences were confirmed by microfluidic card PCR technology.

resultsThe most complex genetic regulation in the retina was observed in ZDF rats with a strong overlap to STZ-Wistar rats. Surprisingly, systemic insulin resistance alone in ZF rats without concomitant hyperglycemia did not induce any significant change in retinal gene expression pattern. Pathway analysis indicate an overlap between ZDF rats and STZ-treated rats in pathways like complement system activation, acute phase response signalling, and oncostatin-M signalling. Major array gene expression changes could be confirmed by subsequent PCR. An analysis of upstream transcriptional regulators revealed interferon-γ, interleukin-6 and oncostatin-M in STZ and ZDF rats.

conclusionsSystemic hyperinsulinaemia without hyperglycemia does not result in significant gene expression changes in retina. In contrast, persistent systemic hyperglycemia boosts much stronger expression changes with a limited number of known and new key regulators.

Indexed as

Gene Expression RegulationInsulin ResistanceAcute-Phase ProteinsAnimalsComplement ActivationDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Diabetic RetinopathyEye ProteinsGene Expression ProfilingHyperglycemiaHyperinsulinismMaleOncostatin MRats, Mutant StrainsRats, WistarAcute-Phase ProteinsEye ProteinsOncostatin M

Identifiers

PMID28575111
PMCPMC5456117
OpenAlexW2621066206

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.