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Release of GLP-1 and PYY in response to the activation of G protein-coupled bile acid receptor TGR5 is mediated by Epac/PLC-ε pathway and modulated by endogenous H2S

Overview of attention for article published in Frontiers in Physiology, November 2014
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Title
Release of GLP-1 and PYY in response to the activation of G protein-coupled bile acid receptor TGR5 is mediated by Epac/PLC-ε pathway and modulated by endogenous H2S
Published in
Frontiers in Physiology, November 2014
DOI 10.3389/fphys.2014.00420
Pubmed ID
Authors

Vanitha Bala, Senthilkumar Rajagopal, Divya P. Kumar, Ancy D. Nalli, Sunila Mahavadi, Arun J. Sanyal, John R. Grider, Karnam S. Murthy

Abstract

Activation of plasma membrane TGR5 receptors in enteroendocrine cells by bile acids is known to regulate gastrointestinal secretion and motility and glucose homeostasis. The endocrine functions of the gut are modulated by microenvironment of the distal gut predominantly by sulfur-reducing bacteria of the microbiota that produce H2S. However, the mechanisms involved in the release of peptide hormones, GLP-1 and PYY in response to TGR5 activation by bile acids and the effect of H2S on bile acid-induced release of GLP-1 and PYY are unclear. In the present study, we have identified the signaling pathways activated by the bile acid receptor TGR5 to mediate GLP-1 and PYY release and the mechanism of inhibition of their release by H2S in enteroendocrine cells. The TGR5 ligand oleanolic acid (OA) stimulated Gαs and cAMP formation, and caused GLP-1 and PYY release. OA-induced cAMP formation and peptide release were blocked by TGR5 siRNA. OA also caused an increase in PI hydrolysis and intracellular Ca(2+). Increase in PI hydrolysis was abolished in cells transfected with PLC-ε siRNA. 8-pCPT-2'-O-Me-cAMP, a selective activator of Epac, stimulated PI hydrolysis, and GLP-1 and PYY release. L-Cysteine, which activates endogenous H2S producing enzymes cystathionine-γ-lyase and cystathionine-β-synthase, and NaHS and GYY4137, which generate H2S, inhibited PI hydrolysis and GLP-1 and PYY release in response to OA or 8-pCPT-2'-O-Me-cAMP. Propargylglycine, an inhibitor of CSE, reversed the effect of L-cysteine on PI hydrolysis and GLP-1 and PYY release. We conclude: (i) activation of Gαs-coupled TGR5 receptors causes stimulation of PI hydrolysis, and release of GLP-1 and PYY via a PKA-independent, cAMP-dependent mechanism involving Epac/PLC-ε/Ca(2+) pathway, and (ii) H2S has potent inhibitory effects on GLP-1 and PYY release in response to TGR5 activation, and the mechanism involves inhibition of PLC-ε/Ca(2+) pathway.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 112 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 2 2%
Japan 1 <1%
Denmark 1 <1%
Unknown 108 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 18%
Student > Bachelor 19 17%
Researcher 12 11%
Student > Master 12 11%
Student > Doctoral Student 6 5%
Other 19 17%
Unknown 24 21%
Readers by discipline Count As %
Agricultural and Biological Sciences 24 21%
Medicine and Dentistry 21 19%
Biochemistry, Genetics and Molecular Biology 16 14%
Immunology and Microbiology 4 4%
Pharmacology, Toxicology and Pharmaceutical Science 4 4%
Other 11 10%
Unknown 32 29%
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 19 November 2014.
All research outputs
#18,382,900
of 22,769,322 outputs
Outputs from Frontiers in Physiology
#8,094
of 13,560 outputs
Outputs of similar age
#187,738
of 262,158 outputs
Outputs of similar age from Frontiers in Physiology
#59
of 119 outputs
Altmetric has tracked 22,769,322 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,560 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.5. This one is in the 31st percentile – i.e., 31% 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 262,158 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 119 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.