Metformin Inhibits Expression and Secretion of PEDF in Adipocyte and Hepatocyte via Promoting AMPK Phosphorylation
Objective. Pigment epithelium-derived factor (PEDF) plays an important role in obesity-induced insulin resistance (IR). The study aims to investigate the effect of metformin, a widely used agent to improve IR, on PEDF production both in vivo and in vitro. Methods. SD rats were divided into normal co...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/429207 |
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| author | Shumin Yang Qiong Lv Ting Luo Lulu Liu Rufei Gao Shumei Chen Peng Ye Qingfeng Cheng Qifu Li |
| author_facet | Shumin Yang Qiong Lv Ting Luo Lulu Liu Rufei Gao Shumei Chen Peng Ye Qingfeng Cheng Qifu Li |
| author_sort | Shumin Yang |
| collection | DOAJ |
| description | Objective. Pigment epithelium-derived factor (PEDF) plays an important role in obesity-induced insulin resistance (IR). The study aims to investigate the effect of metformin, a widely used agent to improve IR, on PEDF production both in vivo and in vitro. Methods. SD rats were divided into normal control group, high fat group (HF group), and metformin group (MET group). Hyperinsulinemic euglycemic clamp was performed to evaluate insulin sensitivity. IR models of 3T3-L1 and HepG2 cells were established and then treated with metformin and inhibitor of AMP activated protein kinase (AMPK). Results. In vivo, the HF group showed increased serum PEDF which is negatively correlated with insulin sensitivity, while the MET group revealed decreased serum PEDF and downregulated PEDF expression in fat and liver, concomitant with significantly improved IR. In vitro, the IR cells showed enhanced PEDF secretion and expression, whereas metformin lowered PEDF secretion and expression, accompanied with increased glucose uptake. Metformin stimulated AMPK phosphorylation in fat and liver of the obese rats, while in vitro, when combined with AMPK inhibitor, the effect of metformin on PEDF was abrogated. Conclusions. Metformin inhibits the expression and secretion of PEDF in fat and liver via promoting AMPK phosphorylation, which is closely associated with IR improvement. |
| format | Article |
| id | doaj-art-a27b64f2faa943e79fda431ff98f5303 |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-a27b64f2faa943e79fda431ff98f53032025-08-20T02:20:19ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/429207429207Metformin Inhibits Expression and Secretion of PEDF in Adipocyte and Hepatocyte via Promoting AMPK PhosphorylationShumin Yang0Qiong Lv1Ting Luo2Lulu Liu3Rufei Gao4Shumei Chen5Peng Ye6Qingfeng Cheng7Qifu Li8Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Street, Chongqing 400016, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Street, Chongqing 400016, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Street, Chongqing 400016, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Street, Chongqing 400016, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Street, Chongqing 400016, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Street, Chongqing 400016, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Street, Chongqing 400016, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Street, Chongqing 400016, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Street, Chongqing 400016, ChinaObjective. Pigment epithelium-derived factor (PEDF) plays an important role in obesity-induced insulin resistance (IR). The study aims to investigate the effect of metformin, a widely used agent to improve IR, on PEDF production both in vivo and in vitro. Methods. SD rats were divided into normal control group, high fat group (HF group), and metformin group (MET group). Hyperinsulinemic euglycemic clamp was performed to evaluate insulin sensitivity. IR models of 3T3-L1 and HepG2 cells were established and then treated with metformin and inhibitor of AMP activated protein kinase (AMPK). Results. In vivo, the HF group showed increased serum PEDF which is negatively correlated with insulin sensitivity, while the MET group revealed decreased serum PEDF and downregulated PEDF expression in fat and liver, concomitant with significantly improved IR. In vitro, the IR cells showed enhanced PEDF secretion and expression, whereas metformin lowered PEDF secretion and expression, accompanied with increased glucose uptake. Metformin stimulated AMPK phosphorylation in fat and liver of the obese rats, while in vitro, when combined with AMPK inhibitor, the effect of metformin on PEDF was abrogated. Conclusions. Metformin inhibits the expression and secretion of PEDF in fat and liver via promoting AMPK phosphorylation, which is closely associated with IR improvement.http://dx.doi.org/10.1155/2013/429207 |
| spellingShingle | Shumin Yang Qiong Lv Ting Luo Lulu Liu Rufei Gao Shumei Chen Peng Ye Qingfeng Cheng Qifu Li Metformin Inhibits Expression and Secretion of PEDF in Adipocyte and Hepatocyte via Promoting AMPK Phosphorylation Mediators of Inflammation |
| title | Metformin Inhibits Expression and Secretion of PEDF in Adipocyte and Hepatocyte via Promoting AMPK Phosphorylation |
| title_full | Metformin Inhibits Expression and Secretion of PEDF in Adipocyte and Hepatocyte via Promoting AMPK Phosphorylation |
| title_fullStr | Metformin Inhibits Expression and Secretion of PEDF in Adipocyte and Hepatocyte via Promoting AMPK Phosphorylation |
| title_full_unstemmed | Metformin Inhibits Expression and Secretion of PEDF in Adipocyte and Hepatocyte via Promoting AMPK Phosphorylation |
| title_short | Metformin Inhibits Expression and Secretion of PEDF in Adipocyte and Hepatocyte via Promoting AMPK Phosphorylation |
| title_sort | metformin inhibits expression and secretion of pedf in adipocyte and hepatocyte via promoting ampk phosphorylation |
| url | http://dx.doi.org/10.1155/2013/429207 |
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