Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation
Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 ce...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/9073037 |
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| author | Jia You Zai Wang Shiqing Xu Wenjian Zhang Qing Fang Honglin Liu Liang Peng Tingting Deng Jinning Lou |
| author_facet | Jia You Zai Wang Shiqing Xu Wenjian Zhang Qing Fang Honglin Liu Liang Peng Tingting Deng Jinning Lou |
| author_sort | Jia You |
| collection | DOAJ |
| description | Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway. |
| format | Article |
| id | doaj-art-0b8a09594c0c45e19f0ca103f32dddef |
| institution | OA Journals |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-0b8a09594c0c45e19f0ca103f32dddef2025-08-20T02:03:28ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/90730379073037Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK ActivationJia You0Zai Wang1Shiqing Xu2Wenjian Zhang3Qing Fang4Honglin Liu5Liang Peng6Tingting Deng7Jinning Lou8Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaAdvanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway.http://dx.doi.org/10.1155/2016/9073037 |
| spellingShingle | Jia You Zai Wang Shiqing Xu Wenjian Zhang Qing Fang Honglin Liu Liang Peng Tingting Deng Jinning Lou Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation Journal of Diabetes Research |
| title | Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation |
| title_full | Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation |
| title_fullStr | Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation |
| title_full_unstemmed | Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation |
| title_short | Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation |
| title_sort | advanced glycation end products impair glucose stimulated insulin secretion of a pancreatic β cell line ins 1 3 by disturbance of microtubule cytoskeleton via p38 mapk activation |
| url | http://dx.doi.org/10.1155/2016/9073037 |
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