Evidence mapPaperPMID 35867787Full record

ArticleScience advances2022

14-3-3-zeta mediates GLP-1 receptor agonist action to alter α cell proglucagon processing.

Marlena M Holter, Daryl J Phuong, Isaac Lee, Mridusmita Saikia, Lisa Weikert, Samantha Fountain, Elizabeth T Anderson, Qin Fu, Sheng Zhang, Kyle W Sloop and 1 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.0field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Marlena M HolterDepartment of Biomedical Sciences, Cornell University, College of Veterinary Medicine, Ithaca, NY, USA.ORCID 0000-0002-1748-5409
Daryl J PhuongDepartment of Biomedical Sciences, Cornell University, College of Veterinary Medicine, Ithaca, NY, USA.ORCID 0000-0003-4049-8694
Isaac LeeDepartment of Biomedical Sciences, Cornell University, College of Veterinary Medicine, Ithaca, NY, USA.ORCID 0000-0003-1371-8364
Mridusmita SaikiaDepartment of Biomedical Sciences, Cornell University, College of Veterinary Medicine, Ithaca, NY, USA.ORCID 0000-0002-5848-3303
Lisa WeikertDepartment of Biomedical Sciences, Cornell University, College of Veterinary Medicine, Ithaca, NY, USA.ORCID 0000-0003-0371-372X
Samantha FountainDepartment of Biomedical Sciences, Cornell University, College of Veterinary Medicine, Ithaca, NY, USA.
Elizabeth T AndersonProteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, USA.
Qin FuProteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, USA.ORCID 0000-0003-4944-772X
Sheng ZhangProteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, USA.ORCID 0000-0001-8206-1007
Kyle W SloopDiabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.ORCID 0000-0001-6748-9929
Bethany P CummingsDepartment of Biomedical Sciences, Cornell University, College of Veterinary Medicine, Ithaca, NY, USA.ORCID 0000-0002-0610-9870
Cornell University · USEli Lilly (United States) · US

Funding

NYR-Diabetes Research Center (NYR-DRC)P30DK020541 · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2025 to 2025
$2.4M
NIDDK NIH HHS F30 DK126538NIDDK NIH HHS P30 DK020541NIDDK NIH HHS R56 DK124853NIDDK NIH HHS UC4 DK098085NIH HHS S10 OD017992NIH HHS T35 OD010941
6 · The paper itself

Abstract

Recent studies demonstrate that α cells contribute to glucose-stimulated insulin secretion (GSIS). Glucagon-like peptide-1 receptor (GLP-1R) agonists potently potentiate GSIS, making these drugs useful for diabetes treatment. However, the role of α and β cell paracrine interactions in the effects of GLP-1R agonists is undefined. We previously found that increased β cell GLP-1R signaling activates α cell GLP-1 expression. Here, we characterized the bidirectional paracrine cross-talk by which α and β cells communicate to mediate the effects of the GLP-1R agonist, liraglutide. We find that the effect of liraglutide to enhance GSIS is blunted by α cell ablation in male mice. Furthermore, the effect of β cell GLP-1R signaling to activate α cell GLP-1 is mediated by a secreted protein factor that is regulated by the signaling protein, 14-3-3-zeta, in mouse and human islets. These data refine our understanding of GLP-1 pharmacology and identify 14-3-3-zeta as a potential target to enhance α cell GLP-1 production.

Identifiers

PMID35867787
PMCPMC9307243
OpenAlexW4286587183

What Socratic holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.