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Transcription factor Ets-1 links glucotoxicity to pancreatic beta cell dysfunction through inhibiting PDX-1 expression in rodent models

Overview of attention for article published in Diabetologia, November 2015
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Title
Transcription factor Ets-1 links glucotoxicity to pancreatic beta cell dysfunction through inhibiting PDX-1 expression in rodent models
Published in
Diabetologia, November 2015
DOI 10.1007/s00125-015-3805-3
Pubmed ID
Authors

Fang Chen, Min Sha, Yanyang Wang, Tijun Wu, Wei Shan, Jia Liu, Wenbo Zhou, Yunxia Zhu, Yujie Sun, Yuguang Shi, David Bleich, Xiao Han

Abstract

'Glucotoxicity' is a term used to convey the negative effect of hyperglycaemia on beta cell function; however, the underlying molecular mechanisms that impair insulin secretion and gene expression are poorly defined. Our objective was to define the role of transcription factor v-ets avian erythroblastosis virus E26 oncogene homologue 1 (Ets-1) in beta cell glucotoxicity. Primary islets and Min6 cells were exposed to high glucose and Ets-1 expression was measured. Recombinant adenovirus and transgenic mice were used to upregulate Ets-1 expression in beta cells in vitro and in vivo, and insulin secretion was assessed. The binding activity of H3/H4 histone on the Ets-1 promoter, and that of forkhead box (FOX)A2, FOXO1 and Ets-1 on the Pdx-1 promoter was measured by chromatin immunoprecipitation and quantitative real-time PCR assay. High glucose induced upregulation of Ets-1 expression and hyperacetylation of histone H3 and H4 at the Ets-1 gene promoter in beta cells. Ets-1 overexpression dramatically suppressed insulin secretion and biosynthesis both in vivo and in vitro. Besides, Ets-1 overexpression increased the activity of FOXO1 but decreased that of FOXA2 binding to the pancreatic and duodenal homeobox 1 (PDX-1) homology region 2 (PH2), resulting in inhibition of Pdx-1 promoter activity and downregulation of PDX-1 expression and activity. In addition, high glucose promoted the interaction of Ets-1 and FOXO1, and the activity of Ets-1 binding to the Pdx-1 promoter. Importantly, PDX-1 overexpression reversed the defect in pancreatic beta cells induced by Ets-1 excess, while knockdown of Ets-1 prevented hyperglycaemia-induced dysfunction of pancreatic beta cells. Our observations suggest that Ets-1 links glucotoxicity to pancreatic beta cell dysfunction through inhibiting PDX-1 expression in type 2 diabetes.

X Demographics

X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 29%
Student > Bachelor 5 16%
Student > Doctoral Student 2 6%
Researcher 2 6%
Student > Master 2 6%
Other 4 13%
Unknown 7 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 26%
Agricultural and Biological Sciences 5 16%
Medicine and Dentistry 3 10%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Veterinary Science and Veterinary Medicine 1 3%
Other 2 6%
Unknown 11 35%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 25 January 2016.
All research outputs
#14,700,486
of 22,833,393 outputs
Outputs from Diabetologia
#4,370
of 5,035 outputs
Outputs of similar age
#153,845
of 282,576 outputs
Outputs of similar age from Diabetologia
#50
of 68 outputs
Altmetric has tracked 22,833,393 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,035 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.7. This one is in the 12th percentile – i.e., 12% 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 282,576 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 68 others from the same source and published within six weeks on either side of this one. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.