Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis
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 Ca2+...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319305997 |
| _version_ | 1811231016004616192 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ju-Young Kim |
| collection | DOAJ |
| description | 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 Ca2+ 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 antiapoptotic 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 Ca2+-ATPase (SERCA) 2/3 was determined by real-time PCR and western blot analysis. Chronic exposure to glibenclamide increased apoptosis by depletion of ER Ca2+ concentration through reduced expression of SERCA 2/3. Pretreatment with Exendin-4 had an anti-apoptotic role through ER stress modulation and ER Ca2+ 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. Keywords:: endoplasmic reticulum (ER) calcium depletion, apoptosis, ER stress, glucagon like peptide-1(GLP-1), sulfonylurea |
| first_indexed | 2024-04-12T10:39:03Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T10:39:03Z |
| publishDate | 2012-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-3e8613daa9944238a7651a143a9b90712022-12-22T03:36:39ZengElsevierJournal of Pharmacological Sciences1347-86132012-01-0111816574Exendin-4 Protects Against Sulfonylurea-Induced β-Cell ApoptosisJu-Young Kim0Dong-Mee Lim1Hyung-Seo Park2Chan-Il Moon3Kyung-Jin Choi4Seong-Kyu Lee5Haing-Woon Baik6Keun-Young Park7Byung-Joon Kim8Division of Endocrinology and Metabolism, Department of Internal Medicine, Daejeon 302-832, KoreaDivision of Endocrinology and Metabolism, Department of Internal Medicine, Daejeon 302-832, KoreaDepartment of Physiology, Konyang University School of Medicine, Daejeon 302-832, KoreaDepartment of Cardiology, Gachon University of Medicine and Science, Incheon 406-799, KoreaDepartment of Physiology, Konyang University School of Medicine, Daejeon 302-832, KoreaDepartment of Biochemistry and Molecular Biology, Eulji University School of Medicine, Daejeon 301-746, KoreaDepartment of Biochemistry and Molecular Biology, Eulji University School of Medicine, Daejeon 301-746, KoreaDivision of Endocrinology and Metabolism, Department of Internal Medicine, Daejeon 302-832, KoreaDivision of Endocrinology and Metabolism, Department of Internal Medicine, Daejeon 302-832, Korea; Myunggok Medical Research Institute, Konyang University School of Medicine, Daejeon 302-832, Korea; Corresponding author. kbjoon4u@hananet.netSulfonylurea 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 Ca2+ 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 antiapoptotic 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 Ca2+-ATPase (SERCA) 2/3 was determined by real-time PCR and western blot analysis. Chronic exposure to glibenclamide increased apoptosis by depletion of ER Ca2+ concentration through reduced expression of SERCA 2/3. Pretreatment with Exendin-4 had an anti-apoptotic role through ER stress modulation and ER Ca2+ 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. Keywords:: endoplasmic reticulum (ER) calcium depletion, apoptosis, ER stress, glucagon like peptide-1(GLP-1), sulfonylureahttp://www.sciencedirect.com/science/article/pii/S1347861319305997 |
| spellingShingle | 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 Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis Journal of Pharmacological Sciences |
| title | Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis |
| title_full | Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis |
| title_fullStr | Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis |
| title_full_unstemmed | Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis |
| title_short | Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis |
| title_sort | exendin 4 protects against sulfonylurea induced β cell apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319305997 |
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