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ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes

Jonathon Davies, Steve Bain, Venkat Kanamarlapudi Orcid Logo

BIOCHEMICAL PHARMACOLOGY, Volume: 90, Issue: 4, Pages: 406 - 413

Swansea University Author: Venkat Kanamarlapudi Orcid Logo

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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...

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Published in: BIOCHEMICAL PHARMACOLOGY
Published: 2014
URI: https://cronfa.swan.ac.uk/Record/cronfa18415
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first_indexed 2014-09-14T01:58:39Z
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spelling 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 BMS 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 Biomedical Sciences COLLEGE CODE BMS 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
author_id_str_mv 63741801137148abfa4c00cd547dcdfa
author_id_fullname_str_mv 63741801137148abfa4c00cd547dcdfa_***_Venkat Kanamarlapudi
author Venkat Kanamarlapudi
author2 Jonathon Davies
Steve Bain
Venkat Kanamarlapudi
format Journal article
container_title BIOCHEMICAL PHARMACOLOGY
container_volume 90
container_issue 4
container_start_page 406
publishDate 2014
institution Swansea University
doi_str_mv 10.1016/j.bcp.2014.06.012
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 0
active_str 0
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 2014-08-15T03:21:35Z
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score 11.017016

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