| The prostaglandin E2 receptor, EP3, is induced in diabetic islets and negatively regulates glucose- and hormone-stimulated insulin secretion. | |
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MedLine Citation:
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PMID: 23349487 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BTBR mice develop severe diabetes in response to genetically-induced obesity due to a failure of the β-cells to compensate for peripheral insulin resistance. In analyzing BTBR islet gene expression patterns, we observed that the gene for the EP3 isoform of the prostaglandin E2 (PGE2) receptor, Ptger3, was upregulated with diabetes. The EP3 receptor couples to G proteins of the Gi subfamily to decrease intracellular cyclic AMP (cAMP), blunting glucose-stimulated insulin secretion (GSIS). Also upregulated were several genes involved in the synthesis of PGE2. We hypothesized that increased signaling through EP3 might be coincident with the development of diabetes and contribute to β-cell dysfunction. We confirmed that the PGE2-to-EP3 signaling pathway was active in islets from confirmed diabetic BTBR mice and human cadaveric donors, with increased EP3 expression, PGE2 production, and function of EP3 agonists and antagonists to modulate cAMP production and GSIS. We also analyzed the impact of EP3 receptor activation on signaling through the glucagon-like peptide 1 (GLP-1) receptor. We demonstrated that EP3 agonists antagonize GLP-1 signaling, decreasing the maximal effect that GLP-1 can elicit on cAMP production and GSIS. Taken together, our results identify EP3 as a new therapeutic target for β-cell dysfunction in T2D. |
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Authors:
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Michelle E Kimple; Mark P Keller; Mary R Rabaglia; Renee L Pasker; Nathan A Truchan; Joshua C Neuman; Harpreet K Brar; Alan D Attie |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-24 |
Journal Detail:
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Title: Diabetes Volume: - ISSN: 1939-327X ISO Abbreviation: Diabetes Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Wisconsin-Madison, Medicine, Division of Endocrinology, Diabetes, and Metabolism, 4th Floor, Medical Foundation Centennial Building, Madison, Wisconsin, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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