| Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis. | |
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MedLine Citation:
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PMID: 22186619 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from β-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by β-cell exhaustion and apoptosis. ER stress induced by Ca(2+) depletion in endoplasmic reticulum (ER) is speculated be one of the causes of secondary failure, but it remains unclear. Glucagon like peptide-1 (GLP-1) has anti-apoptotic effects in β-cells after the induction of oxidative and ER stress. In this study, we examined the anti-apoptotic action of a GLP-1 analogue in β-cell lines and islets against ER stress induced by chronic treatment of sulfonylurea. HIT-T15 and dispersed islet cells were exposed to glibenclamide for 48 h, and apoptosis was evaluated using Annexin/PI flow cytometry. Expression of the ER stress-related molecules and sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) 2/3 was determined by real-time PCR and western blot analysis. Chronic exposure to glibenclamide increased apoptosis by depletion of ER Ca(2+) concentration through reduced expression of SERCA 2/3. Pretreatment with Exendin-4 had an anti-apoptotic role through ER stress modulation and ER Ca(2+) replenishing by SERCA restoration. These findings will further the understanding of one cause of glibenclamide-induced β-cell loss and therapeutic availability of GLP-1-based drugs in secondary failure by sulfonylurea during treatment of diabetes. |
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Authors:
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Ju-Young Kim; Dong-Mee Lim; Hyung-Seo Park; Chan-Il Moon; Kyung-Jin Choi; Seong-Kyu Lee; Haing-Woon Baik; Keun-Young Park; Byung-Joon Kim |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-21 |
Journal Detail:
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Title: Journal of pharmacological sciences Volume: - ISSN: 1347-8648 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101167001 Medline TA: J Pharmacol Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Endocrinology and Metabolism, Department of Internal Medicine, Konyang University School of Medicine, Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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