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TCF1 links GIPR signaling to the control of beta cell function and survival

Overview of attention for article published in Nature Medicine, December 2015
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (94th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (51st percentile)

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Title
TCF1 links GIPR signaling to the control of beta cell function and survival
Published in
Nature Medicine, December 2015
DOI 10.1038/nm.3997
Pubmed ID
Authors

Jonathan E Campbell, John R Ussher, Erin E Mulvihill, Jelena Kolic, Laurie L Baggio, Xiemen Cao, Yu Liu, Benjamin J Lamont, Tsukasa Morii, Catherine J Streutker, Natalia Tamarina, Louis H Philipson, Jeffrey L Wrana, Patrick E MacDonald, Daniel J Drucker

Abstract

The glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor transduce nutrient-stimulated signals to control beta cell function. Although the GLP-1 receptor (GLP-1R) is a validated drug target for diabetes, the importance of the GIP receptor (GIPR) for the function of beta cells remains uncertain. We demonstrate that mice with selective ablation of GIPR in beta cells (MIP-Cre:Gipr(Flox/Flox); Gipr(-/-βCell)) exhibit lower levels of meal-stimulated insulin secretion, decreased expansion of adipose tissue mass and preservation of insulin sensitivity when compared to MIP-Cre controls. Beta cells from Gipr(-/-βCell) mice display greater sensitivity to apoptosis and markedly lower islet expression of T cell-specific transcription factor-1 (TCF1, encoded by Tcf7), a protein not previously characterized in beta cells. GIP, but not GLP-1, promotes beta cell Tcf7 expression via a cyclic adenosine monophosphate (cAMP)-independent and extracellular signal-regulated kinase (ERK)-dependent pathway. Tcf7 (in mice) or TCF7 (in humans) levels are lower in islets taken from diabetic mice and in humans with type 2 diabetes; knockdown of TCF7 in human and mouse islets impairs the cytoprotective responsiveness to GIP and enhances the magnitude of apoptotic injury, whereas restoring TCF1 levels in beta cells from Gipr(-/-βCell) mice lowers the number of apoptotic cells compared to that seen in MIP-Cre controls. Tcf7(-/-) mice show impaired insulin secretion, deterioration of glucose tolerance with either aging and/or high-fat feeding and increased sensitivity to beta cell injury relative to wild-type (WT) controls. Hence the GIPR-TCF1 axis represents a potential therapeutic target for preserving both the function and survival of vulnerable, diabetic beta cells.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 77 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 1%
India 1 1%
Russia 1 1%
Japan 1 1%
United States 1 1%
Unknown 72 94%

Demographic breakdown

Readers by professional status Count As %
Researcher 24 31%
Student > Ph. D. Student 16 21%
Student > Master 10 13%
Professor 6 8%
Professor > Associate Professor 5 6%
Other 10 13%
Unknown 6 8%
Readers by discipline Count As %
Medicine and Dentistry 20 26%
Biochemistry, Genetics and Molecular Biology 17 22%
Agricultural and Biological Sciences 16 21%
Immunology and Microbiology 5 6%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Other 6 8%
Unknown 10 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 29. 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 18 March 2021.
All research outputs
#847,424
of 17,464,602 outputs
Outputs from Nature Medicine
#1,892
of 7,485 outputs
Outputs of similar age
#21,316
of 373,394 outputs
Outputs of similar age from Nature Medicine
#38
of 76 outputs
Altmetric has tracked 17,464,602 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 7,485 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 68.7. This one has gotten more attention than average, scoring higher than 74% 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 373,394 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 94% of its contemporaries.
We're also able to compare this research output to 76 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.