PEDF attenuates insulin-dependent molecular pathways of glucose homeostasis in skeletal myocytes
Pigment epithelium-derived factor (PEDF) is an anti-angiogenic serpin associated with insulin resistance in metabolic disorders such as diabetes, metabolic syndrome, obesity and polycystic ovarian syndrome. While the mechanism of PEDF induced-insulin resistance of metabolic disorders has been attrib...
| Main Authors: | , , |
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| Format: | Journal Article |
| Published: |
2015
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| Online Access: | http://hdl.handle.net/20.500.11937/42748 |
| _version_ | 1848756504520294400 |
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| author | Carnagarin, R. Dharmarajan, Arunasalam Dass, Crispin |
| author_facet | Carnagarin, R. Dharmarajan, Arunasalam Dass, Crispin |
| author_sort | Carnagarin, R. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Pigment epithelium-derived factor (PEDF) is an anti-angiogenic serpin associated with insulin resistance in metabolic disorders such as diabetes, metabolic syndrome, obesity and polycystic ovarian syndrome. While the mechanism of PEDF induced-insulin resistance of metabolic disorders has been attributed to its inflammatory and lipolytic effects, little evidence exists to support a direct role of PEDF in mediating insulin resistance. Here, we seminally provide evidence that PEDF can inhibit insulin signal transduction governing glucose homeostasis from the receptor to the effector phosphorylation through Akt/PKB-dependent and -independent pathways in mouse and human skeletal muscle cell lines. PEDF attenuates the insulin-dependent molecular axes of glucose metabolism. Exposure of skeletal myocytes to PEDF attenuates insulin-dependent insulin receptor autophosphorylation, tyrosine phosphorylation of insulin receptor substrate 1, and dual loop phosphorylation-activation of Akt. PEDF significantly inhibits the downstream effector - glycogen synthase kinase (and thereby the glycogenic axis of insulin signalling). PEDF turned off both the molecular switches of GLUT4 translocation: IRS-Akt/PKB-AS160 mediated and IR-pCbl-dependent GLUT4 translocation (the molecular axis of glucose uptake). These findings implicate a direct effect of PEDF on multiple insulin-dependent molecular mechanisms of glucose homeostasis in skeletal muscle cells, thereby enabling it to contribute to peripheral insulin resistance at the cellular level. |
| first_indexed | 2025-11-14T09:13:15Z |
| format | Journal Article |
| id | curtin-20.500.11937-42748 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:13:15Z |
| publishDate | 2015 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-427482017-09-13T15:04:46Z PEDF attenuates insulin-dependent molecular pathways of glucose homeostasis in skeletal myocytes Carnagarin, R. Dharmarajan, Arunasalam Dass, Crispin Pigment epithelium-derived factor (PEDF) is an anti-angiogenic serpin associated with insulin resistance in metabolic disorders such as diabetes, metabolic syndrome, obesity and polycystic ovarian syndrome. While the mechanism of PEDF induced-insulin resistance of metabolic disorders has been attributed to its inflammatory and lipolytic effects, little evidence exists to support a direct role of PEDF in mediating insulin resistance. Here, we seminally provide evidence that PEDF can inhibit insulin signal transduction governing glucose homeostasis from the receptor to the effector phosphorylation through Akt/PKB-dependent and -independent pathways in mouse and human skeletal muscle cell lines. PEDF attenuates the insulin-dependent molecular axes of glucose metabolism. Exposure of skeletal myocytes to PEDF attenuates insulin-dependent insulin receptor autophosphorylation, tyrosine phosphorylation of insulin receptor substrate 1, and dual loop phosphorylation-activation of Akt. PEDF significantly inhibits the downstream effector - glycogen synthase kinase (and thereby the glycogenic axis of insulin signalling). PEDF turned off both the molecular switches of GLUT4 translocation: IRS-Akt/PKB-AS160 mediated and IR-pCbl-dependent GLUT4 translocation (the molecular axis of glucose uptake). These findings implicate a direct effect of PEDF on multiple insulin-dependent molecular mechanisms of glucose homeostasis in skeletal muscle cells, thereby enabling it to contribute to peripheral insulin resistance at the cellular level. 2015 Journal Article http://hdl.handle.net/20.500.11937/42748 10.1016/j.mce.2015.12.010 restricted |
| spellingShingle | Carnagarin, R. Dharmarajan, Arunasalam Dass, Crispin PEDF attenuates insulin-dependent molecular pathways of glucose homeostasis in skeletal myocytes |
| title | PEDF attenuates insulin-dependent molecular pathways of glucose homeostasis in skeletal myocytes |
| title_full | PEDF attenuates insulin-dependent molecular pathways of glucose homeostasis in skeletal myocytes |
| title_fullStr | PEDF attenuates insulin-dependent molecular pathways of glucose homeostasis in skeletal myocytes |
| title_full_unstemmed | PEDF attenuates insulin-dependent molecular pathways of glucose homeostasis in skeletal myocytes |
| title_short | PEDF attenuates insulin-dependent molecular pathways of glucose homeostasis in skeletal myocytes |
| title_sort | pedf attenuates insulin-dependent molecular pathways of glucose homeostasis in skeletal myocytes |
| url | http://hdl.handle.net/20.500.11937/42748 |