Journal article 1205 views
ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes
BIOCHEMICAL PHARMACOLOGY, Volume: 90, Issue: 4, Pages: 406 - 413
Swansea University Author: Venkat Kanamarlapudi
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DOI (Published version): 10.1016/j.bcp.2014.06.012
Abstract
Endothelin-1 (ET-1) induces lipolysis in adipocytes, where ET-1 chronic exposure results in insulin resistance (IR) through suppression of glucose transporter (GLUT)4 translocation to the plasma membrane and consequently glucose uptake. ARF6 small GTPase, which plays a vital role in cell surface rec...
Published in: | BIOCHEMICAL PHARMACOLOGY |
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2014
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URI: | https://cronfa.swan.ac.uk/Record/cronfa18415 |
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2014-09-14T01:58:39Z |
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2019-06-24T19:28:56Z |
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2019-06-24T14:45:56.3726453 v2 18415 2014-09-13 ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes 63741801137148abfa4c00cd547dcdfa 0000-0002-8739-1483 Venkat Kanamarlapudi Venkat Kanamarlapudi true false 2014-09-13 MEDS Endothelin-1 (ET-1) induces lipolysis in adipocytes, where ET-1 chronic exposure results in insulin resistance (IR) through suppression of glucose transporter (GLUT)4 translocation to the plasma membrane and consequently glucose uptake. ARF6 small GTPase, which plays a vital role in cell surface receptors trafficking, has previously been shown to regulate GLUT4 recycling and thereby insulin signalling. ARF6 also plays a role in ET-1 promoted endothelial cell migration. However, ARF6 involvement in ET-1-induced lipolysis in adipocytes is unknown. Therefore, we investigated the role of ARF6 in ET-1-induced lipolysis in 3T3-L1 adipocytes. This was achieved by studying the effect of inhibitors for the activation of ARF6 and other signalling proteins on ET-1 induced lipolysis and ARF6 activation in the adipocytes. Our results indicate that ET-1 induces, through endothelin type A receptor (ETAR), lipolysis, the ARF6 activation and extracellular-signal regulated kinase (ERK) phosphorylation in adipocytes, further ET-1 stimulated lipolysis is inhibited by the inhibitors of ARF6 activation, ERK phosphorylation and dynamin, which is essential for endocytosis. Our studies also revealed that ARF6 acts upstream of ERK in ET-1-indcued lipolysis. In summary, we determined that ET-1 activation of ETAR signalled through ARF6, which is crucial for lipolysis. (C) 2014 Elsevier Inc. All rights reserved. Journal Article BIOCHEMICAL PHARMACOLOGY 90 4 406 413 15 8 2014 2014-08-15 10.1016/j.bcp.2014.06.012 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University 2019-06-24T14:45:56.3726453 2014-09-13T21:54:26.2416397 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Jonathon Davies 1 Steve Bain 2 Venkat Kanamarlapudi 0000-0002-8739-1483 3 |
title |
ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes |
spellingShingle |
ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes Venkat Kanamarlapudi |
title_short |
ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes |
title_full |
ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes |
title_fullStr |
ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes |
title_full_unstemmed |
ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes |
title_sort |
ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes |
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63741801137148abfa4c00cd547dcdfa |
author_id_fullname_str_mv |
63741801137148abfa4c00cd547dcdfa_***_Venkat Kanamarlapudi |
author |
Venkat Kanamarlapudi |
author2 |
Jonathon Davies Steve Bain Venkat Kanamarlapudi |
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BIOCHEMICAL PHARMACOLOGY |
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90 |
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Swansea University |
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10.1016/j.bcp.2014.06.012 |
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Faculty of Medicine, Health and Life Sciences |
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Faculty of Medicine, Health and Life Sciences |
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Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine |
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description |
Endothelin-1 (ET-1) induces lipolysis in adipocytes, where ET-1 chronic exposure results in insulin resistance (IR) through suppression of glucose transporter (GLUT)4 translocation to the plasma membrane and consequently glucose uptake. ARF6 small GTPase, which plays a vital role in cell surface receptors trafficking, has previously been shown to regulate GLUT4 recycling and thereby insulin signalling. ARF6 also plays a role in ET-1 promoted endothelial cell migration. However, ARF6 involvement in ET-1-induced lipolysis in adipocytes is unknown. Therefore, we investigated the role of ARF6 in ET-1-induced lipolysis in 3T3-L1 adipocytes. This was achieved by studying the effect of inhibitors for the activation of ARF6 and other signalling proteins on ET-1 induced lipolysis and ARF6 activation in the adipocytes. Our results indicate that ET-1 induces, through endothelin type A receptor (ETAR), lipolysis, the ARF6 activation and extracellular-signal regulated kinase (ERK) phosphorylation in adipocytes, further ET-1 stimulated lipolysis is inhibited by the inhibitors of ARF6 activation, ERK phosphorylation and dynamin, which is essential for endocytosis. Our studies also revealed that ARF6 acts upstream of ERK in ET-1-indcued lipolysis. In summary, we determined that ET-1 activation of ETAR signalled through ARF6, which is crucial for lipolysis. (C) 2014 Elsevier Inc. All rights reserved. |
published_date |
2014-08-15T03:36:00Z |
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11.04748 |