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Insulin promotes vascular smooth muscle cell proliferation and apoptosis via differential regulation of tumor necrosis factor‐related apoptosis‐inducing ligand

Overview of attention for article published in Journal of Diabetes, December 2015
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Title
Insulin promotes vascular smooth muscle cell proliferation and apoptosis via differential regulation of tumor necrosis factor‐related apoptosis‐inducing ligand
Published in
Journal of Diabetes, December 2015
DOI 10.1111/1753-0407.12339
Pubmed ID
Authors

Hanis H. Harith, Belinda A. Di Bartolo, Siân P. Cartland, Scott Genner, Mary M. Kavurma

Abstract

Insulin regulates glucose homeostasis but can also promote vascular smooth muscle (VSMC) proliferation and migration important in atherogenesis. We recently showed that TNF-related apoptosis-inducing ligand (TRAIL) promotes intimal thickening, via accelerated growth of VSMCs; whether insulin's effects on VSMCs is dependent on TRAIL is unknown. TRAIL and TRAIL-receptor expression in response to insulin and glucose in VSMCs were determined by PCR. Transcriptional activity was assessed. Transient transfections using wild-type and site-specific mutations of the human TRAIL promoter were assayed. Chromatin immunoprecipitation studies were performed. VSMC proliferation and apoptosis was assessed. Acute insulin and glucose exposure for 24 h stimulated TRAIL mRNA expression in VSMCs. This was also evident at the transcriptional level. Importantly, both insulin and glucose-inducible TRAIL transcription was blocked by dominant-negative Sp1 overexpression. TRAIL has 5 functional Sp1-binding elements (Sp1-1, Sp1-2, Sp-5/6 and Sp1-7). While insulin required Sp1-1 and Sp1-2 sites, glucose needed all Sp1-binding sites on the TRAIL promoter to induce transcription. Furthermore, insulin, but not glucose was able to promote VSMC proliferation over time, associated with increased DcR2 expression. In contrast, chronic 5 d insulin treatment to VSMCs repressed TRAIL and DcR2 expression. Chronic insulin exposure also reduced Sp1 enrichment on the TRAIL promoter and promoted VSMC apoptosis. Here we have identified new mechanistic insight into how TRAIL is regulated by insulin. Our findings may have significant implications at different stages of diabetes associated cardiovascular disease; TRAIL may offer a novel therapeutic solution to combat insulin induced vascular pathologies. This article is protected by copyright. All rights reserved.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 10 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 2 20%
Professor 1 10%
Student > Doctoral Student 1 10%
Unknown 6 60%
Readers by discipline Count As %
Medicine and Dentistry 2 20%
Immunology and Microbiology 1 10%
Unknown 7 70%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 04 September 2015.
All research outputs
#21,966,409
of 24,508,104 outputs
Outputs from Journal of Diabetes
#543
of 649 outputs
Outputs of similar age
#338,801
of 398,288 outputs
Outputs of similar age from Journal of Diabetes
#6
of 8 outputs
Altmetric has tracked 24,508,104 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 649 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.8. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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 398,288 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 8 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.