| {alpha}-Synuclein binds the KATP channel at insulin-secretory granules and inhibits insulin secretion. | |
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MedLine Citation:
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PMID: 20858756 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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α-Synuclein has been studied in numerous cell types often associated with secretory processes. In pancreatic β-cells, α-synuclein might therefore play a similar role by interacting with organelles involved in insulin secretion. We tested for α-synuclein localizing to insulin-secretory granules and characterized its role in glucose-stimulated insulin secretion. Immunohistochemistry and fluorescent sulfonylureas were used to test for α-synuclein localization to insulin granules in β-cells, immunoprecipitation with Western blot analysis for interaction between α-synuclein and K(ATP) channels, and ELISA assays for the effect of altering α-synuclein expression up or down on insulin secretion in INS1 cells or mouse islets, respectively. Differences in cellular phenotype between α-synuclein knockout and wild-type β-cells were found by using confocal microscopy to image the fluorescent insulin biosensor Ins-C-emGFP and by using transmission electron microscopy. The results show that anti-α-synuclein antibodies labeled secretory organelles within β-cells. Anti-α-synuclein antibodies colocalized with K(ATP) channel, anti-insulin, and anti-C-peptide antibodies. α-Synuclein coimmunoprecipitated in complexes with K(ATP) channels. Expression of α-synuclein downregulated insulin secretion at 2.8 mM glucose with little effect following 16.7 mM glucose stimulation. α-Synuclein knockout islets upregulated insulin secretion at 2.8 and 8.4 mM but not 16.7 mM glucose, consistent with the depleted insulin granule density at the β-cell surface membranes observed in these islets. These findings demonstrate that α-synuclein interacts with K(ATP) channels and insulin-secretory granules and functionally acts as a brake on secretion that glucose stimulation can override. α-Synuclein might play similar roles in diabetes as it does in other degenerative diseases, including Alzheimer's and Parkinson's diseases. |
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Authors:
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Xuehui Geng; Haiyan Lou; Jian Wang; Lehong Li; Alexandra L Swanson; Ming Sun; Donna Beers-Stolz; Simon Watkins; Ruth G Perez; Peter Drain |
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Publication Detail:
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Type: Journal Article Date: 2010-09-21 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 300 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E276-86 Citation Subset: IM |
Affiliation:
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Rm. 323 Starzl Biomedical Science Tower, 3500 Terrace St., Pittsburgh, PA 15261. drain@pitt.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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