Exendin-4 Promotes Survival of Mouse Pancreatic β-Cell Line in Lipotoxic Conditions, through the Extracellular Signal-Related Kinase 1/2 Pathway
Type 2 diabetes is a heterogeneous disorder that develops as a result of relatively inappropriate insulin secretion and insulin resistance. Increased levels of free fatty acids (FFAs) are one of the important factors for the pathogenesis of type 2 diabetes and contribute to defective β-cell prolifer...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/5294025 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849685605062017024 |
|---|---|
| author | Jianqiu Gu Qian Wei Hongzhi Zheng Xin Meng Jin Zhang Difei Wang |
| author_facet | Jianqiu Gu Qian Wei Hongzhi Zheng Xin Meng Jin Zhang Difei Wang |
| author_sort | Jianqiu Gu |
| collection | DOAJ |
| description | Type 2 diabetes is a heterogeneous disorder that develops as a result of relatively inappropriate insulin secretion and insulin resistance. Increased levels of free fatty acids (FFAs) are one of the important factors for the pathogenesis of type 2 diabetes and contribute to defective β-cell proliferation and increased β-cell apoptosis. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to possess an antiapoptotic effect, by increasing β-cell mass and improving β-cell function. However, their effects on β-cells in vitro against lipotoxicity have not been elucidated completely. In this study, we investigated whether the GLP-1 receptor agonist exendin-4 displays prosurvival effects in pancreatic β-cells exposed to chronic elevated FFAs. Results showed that exendin-4 inhibited apoptosis induced by palmitate in MIN6 cells. After 24 h of incubation, exendin-4 caused rapid activation of extracellular signal-related kinase 1/2 (ERK1/2) under lipotoxic conditions. The ERK1/2 inhibitor PD98059 blocked the antilipotoxic effect of exendin-4 on MIN6 cells. Exendin-4 also inhibited the mitochondrial pathway of apoptosis. This inhibition is associated with upregulation of BCL-2. Our findings suggested that exendin-4 may exert cytoprotective effects through activation of ERK1/2 and inhibition of the mitochondrial apoptosis pathway. |
| format | Article |
| id | doaj-art-c4e86799180940aaba8d281fe42d62ef |
| institution | DOAJ |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-c4e86799180940aaba8d281fe42d62ef2025-08-20T03:23:03ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/52940255294025Exendin-4 Promotes Survival of Mouse Pancreatic β-Cell Line in Lipotoxic Conditions, through the Extracellular Signal-Related Kinase 1/2 PathwayJianqiu Gu0Qian Wei1Hongzhi Zheng2Xin Meng3Jin Zhang4Difei Wang5Department of Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, ChinaDepartment of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, ChinaDepartment of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, ChinaDepartment of Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, ChinaDepartment of Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, ChinaDepartment of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, ChinaType 2 diabetes is a heterogeneous disorder that develops as a result of relatively inappropriate insulin secretion and insulin resistance. Increased levels of free fatty acids (FFAs) are one of the important factors for the pathogenesis of type 2 diabetes and contribute to defective β-cell proliferation and increased β-cell apoptosis. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to possess an antiapoptotic effect, by increasing β-cell mass and improving β-cell function. However, their effects on β-cells in vitro against lipotoxicity have not been elucidated completely. In this study, we investigated whether the GLP-1 receptor agonist exendin-4 displays prosurvival effects in pancreatic β-cells exposed to chronic elevated FFAs. Results showed that exendin-4 inhibited apoptosis induced by palmitate in MIN6 cells. After 24 h of incubation, exendin-4 caused rapid activation of extracellular signal-related kinase 1/2 (ERK1/2) under lipotoxic conditions. The ERK1/2 inhibitor PD98059 blocked the antilipotoxic effect of exendin-4 on MIN6 cells. Exendin-4 also inhibited the mitochondrial pathway of apoptosis. This inhibition is associated with upregulation of BCL-2. Our findings suggested that exendin-4 may exert cytoprotective effects through activation of ERK1/2 and inhibition of the mitochondrial apoptosis pathway.http://dx.doi.org/10.1155/2016/5294025 |
| spellingShingle | Jianqiu Gu Qian Wei Hongzhi Zheng Xin Meng Jin Zhang Difei Wang Exendin-4 Promotes Survival of Mouse Pancreatic β-Cell Line in Lipotoxic Conditions, through the Extracellular Signal-Related Kinase 1/2 Pathway Journal of Diabetes Research |
| title | Exendin-4 Promotes Survival of Mouse Pancreatic β-Cell Line in Lipotoxic Conditions, through the Extracellular Signal-Related Kinase 1/2 Pathway |
| title_full | Exendin-4 Promotes Survival of Mouse Pancreatic β-Cell Line in Lipotoxic Conditions, through the Extracellular Signal-Related Kinase 1/2 Pathway |
| title_fullStr | Exendin-4 Promotes Survival of Mouse Pancreatic β-Cell Line in Lipotoxic Conditions, through the Extracellular Signal-Related Kinase 1/2 Pathway |
| title_full_unstemmed | Exendin-4 Promotes Survival of Mouse Pancreatic β-Cell Line in Lipotoxic Conditions, through the Extracellular Signal-Related Kinase 1/2 Pathway |
| title_short | Exendin-4 Promotes Survival of Mouse Pancreatic β-Cell Line in Lipotoxic Conditions, through the Extracellular Signal-Related Kinase 1/2 Pathway |
| title_sort | exendin 4 promotes survival of mouse pancreatic β cell line in lipotoxic conditions through the extracellular signal related kinase 1 2 pathway |
| url | http://dx.doi.org/10.1155/2016/5294025 |
| work_keys_str_mv | AT jianqiugu exendin4promotessurvivalofmousepancreaticbcelllineinlipotoxicconditionsthroughtheextracellularsignalrelatedkinase12pathway AT qianwei exendin4promotessurvivalofmousepancreaticbcelllineinlipotoxicconditionsthroughtheextracellularsignalrelatedkinase12pathway AT hongzhizheng exendin4promotessurvivalofmousepancreaticbcelllineinlipotoxicconditionsthroughtheextracellularsignalrelatedkinase12pathway AT xinmeng exendin4promotessurvivalofmousepancreaticbcelllineinlipotoxicconditionsthroughtheextracellularsignalrelatedkinase12pathway AT jinzhang exendin4promotessurvivalofmousepancreaticbcelllineinlipotoxicconditionsthroughtheextracellularsignalrelatedkinase12pathway AT difeiwang exendin4promotessurvivalofmousepancreaticbcelllineinlipotoxicconditionsthroughtheextracellularsignalrelatedkinase12pathway |