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Insulin and IGF1 signalling pathways in human astrocytes in vitro and in vivo; characterisation, subcellular localisation and modulation of the receptors

Overview of attention for article published in Molecular Brain, August 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#22 of 501)
  • High Attention Score compared to outputs of the same age (89th percentile)
  • High Attention Score compared to outputs of the same age and source (94th percentile)

Mentioned by

news
1 news outlet
twitter
7 tweeters
facebook
2 Facebook pages

Citations

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33 Dimensions

Readers on

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103 Mendeley
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Title
Insulin and IGF1 signalling pathways in human astrocytes in vitro and in vivo; characterisation, subcellular localisation and modulation of the receptors
Published in
Molecular Brain, August 2015
DOI 10.1186/s13041-015-0138-6
Pubmed ID
Authors

Claire J. Garwood, Laura E. Ratcliffe, Sarah V. Morgan, Julie E. Simpson, Helen Owens, Irina Vazquez-Villaseñor, Paul R. Heath, Ignacio A. Romero, Paul G. Ince, Stephen B. Wharton

Abstract

The insulin/IGF1 signalling (IIS) pathways are involved in longevity regulation and are dysregulated in neurons in Alzheimer's disease (AD). We previously showed downregulation in IIS gene expression in astrocytes with AD-neuropathology progression, but IIS in astrocytes remains poorly understood. We therefore examined the IIS pathway in human astrocytes and developed models to reduce IIS at the level of the insulin or the IGF1 receptor (IGF1R). We determined IIS was present and functional in human astrocytes by immunoblotting and showed astrocytes express the insulin receptor (IR)-B isoform of Ir. Immunocytochemistry and cell fractionation followed by western blotting revealed the phosphorylation status of insulin receptor substrate (IRS1) affects its subcellular localisation. To validate IRS1 expression patterns observed in culture, expression of key pathway components was assessed on post-mortem AD and control tissue using immunohistochemistry. Insulin signalling was impaired in cultured astrocytes by treatment with insulin + fructose and resulted in decreased IR and Akt phosphorylation (pAkt S473). A monoclonal antibody against IGF1R (MAB391) induced degradation of IGF1R receptor with an associated decrease in downstream pAkt S473. Neither treatment affected cell growth or viability as measured by MTT and Cyquant® assays or GFAP immunoreactivity. IIS is functional in astrocytes. IR-B is expressed in astrocytes which differs from the pattern in neurons, and may be important in differential susceptibility of astrocytes and neurons to insulin resistance. The variable presence of IRS1 in the nucleus, dependent on phosphorylation pattern, suggests the function of signalling molecules is not confined to cytoplasmic cascades. Down-regulation of IR and IGF1R, achieved by insulin + fructose and monoclonal antibody treatments, results in decreased downstream signalling, though the lack of effect on viability suggests that astrocytes can compensate for changes in single pathways. Changes in signalling in astrocytes, as well as in neurons, may be important in ageing and neurodegeneration.

Twitter Demographics

The data shown below were collected from the profiles of 7 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 103 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Mexico 1 <1%
Unknown 102 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 26 25%
Student > Bachelor 21 20%
Student > Master 16 16%
Researcher 15 15%
Student > Doctoral Student 10 10%
Other 10 10%
Unknown 5 5%
Readers by discipline Count As %
Agricultural and Biological Sciences 31 30%
Neuroscience 23 22%
Biochemistry, Genetics and Molecular Biology 16 16%
Medicine and Dentistry 14 14%
Immunology and Microbiology 3 3%
Other 8 8%
Unknown 8 8%

Attention Score in Context

This research output has an Altmetric Attention Score of 14. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 June 2016.
All research outputs
#824,644
of 11,428,083 outputs
Outputs from Molecular Brain
#22
of 501 outputs
Outputs of similar age
#25,328
of 235,889 outputs
Outputs of similar age from Molecular Brain
#1
of 18 outputs
Altmetric has tracked 11,428,083 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 501 research outputs from this source. They receive a mean Attention Score of 4.2. This one has done particularly well, scoring higher than 95% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 235,889 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 18 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 94% of its contemporaries.