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Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells
BACKGROUND: Serotonin (5-HT) improves insulin sensitivity and glucose metabolism, however, the underlying molecular mechanism has remained elusive. Previous studies suggest that 5-HT can activate intracellular small GTPases directly by covalent binding, a process termed serotonylation. Activated sma...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209910/ https://www.ncbi.nlm.nih.gov/pubmed/28053672 http://dx.doi.org/10.1186/s13098-016-0201-1 |
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author | Al-Zoairy, Ramona Pedrini, Michael T. Khan, Mohammad Imran Engl, Julia Tschoner, Alexander Ebenbichler, Christoph Gstraunthaler, Gerhard Salzmann, Karin Bakry, Rania Niederwanger, Andreas |
author_facet | Al-Zoairy, Ramona Pedrini, Michael T. Khan, Mohammad Imran Engl, Julia Tschoner, Alexander Ebenbichler, Christoph Gstraunthaler, Gerhard Salzmann, Karin Bakry, Rania Niederwanger, Andreas |
author_sort | Al-Zoairy, Ramona |
collection | PubMed |
description | BACKGROUND: Serotonin (5-HT) improves insulin sensitivity and glucose metabolism, however, the underlying molecular mechanism has remained elusive. Previous studies suggest that 5-HT can activate intracellular small GTPases directly by covalent binding, a process termed serotonylation. Activated small GTPases have been associated with increased GLUT4 translocation to the cell membrane. Therefore, we investigated whether serotonylation of small GTPases may be involved in improving Insulin sensitivity and glucose metabolism. METHODS: Using fully differentiated L6 rat skeletal muscle cells, we studied the effect of 5-HT in the absence or presence of insulin on glycogen synthesis, glucose uptake and GLUT4 translocation. To prove our L6 model we additionally performed preliminary experiments in C2C12 murine skeletal muscle cells. RESULTS: Incubation with 5-HT led to an increase in deoxyglucose uptake in a concentration-dependent fashion. Accordingly, GLUT4 translocation to the cell membrane and glycogen content were increased. These effects of 5-HT on Glucose metabolism could be augmented by co-incubation with insulin and blunted by co incubation of 5-HT with monodansylcadaverine, an inhibitor of protein serotonylation. In accordance with this observation, incubation with 5-HT resulted in serotonylation of a protein with a molecular weight of approximately 25 kDa. We identified this protein as the small GTPase Rab4, the activity of which has been shown to be stimulated by both insulin signalling and serotonylation. CONCLUSION: Our data suggest that 5-HT elicits its beneficial effects on Glucose metabolism through serotonylation of Rab4, which likely represents the converging point between the insulin and the 5-HT signalling cascades. |
format | Online Article Text |
id | pubmed-5209910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-52099102017-01-04 Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells Al-Zoairy, Ramona Pedrini, Michael T. Khan, Mohammad Imran Engl, Julia Tschoner, Alexander Ebenbichler, Christoph Gstraunthaler, Gerhard Salzmann, Karin Bakry, Rania Niederwanger, Andreas Diabetol Metab Syndr Research BACKGROUND: Serotonin (5-HT) improves insulin sensitivity and glucose metabolism, however, the underlying molecular mechanism has remained elusive. Previous studies suggest that 5-HT can activate intracellular small GTPases directly by covalent binding, a process termed serotonylation. Activated small GTPases have been associated with increased GLUT4 translocation to the cell membrane. Therefore, we investigated whether serotonylation of small GTPases may be involved in improving Insulin sensitivity and glucose metabolism. METHODS: Using fully differentiated L6 rat skeletal muscle cells, we studied the effect of 5-HT in the absence or presence of insulin on glycogen synthesis, glucose uptake and GLUT4 translocation. To prove our L6 model we additionally performed preliminary experiments in C2C12 murine skeletal muscle cells. RESULTS: Incubation with 5-HT led to an increase in deoxyglucose uptake in a concentration-dependent fashion. Accordingly, GLUT4 translocation to the cell membrane and glycogen content were increased. These effects of 5-HT on Glucose metabolism could be augmented by co-incubation with insulin and blunted by co incubation of 5-HT with monodansylcadaverine, an inhibitor of protein serotonylation. In accordance with this observation, incubation with 5-HT resulted in serotonylation of a protein with a molecular weight of approximately 25 kDa. We identified this protein as the small GTPase Rab4, the activity of which has been shown to be stimulated by both insulin signalling and serotonylation. CONCLUSION: Our data suggest that 5-HT elicits its beneficial effects on Glucose metabolism through serotonylation of Rab4, which likely represents the converging point between the insulin and the 5-HT signalling cascades. BioMed Central 2017-01-03 /pmc/articles/PMC5209910/ /pubmed/28053672 http://dx.doi.org/10.1186/s13098-016-0201-1 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Al-Zoairy, Ramona Pedrini, Michael T. Khan, Mohammad Imran Engl, Julia Tschoner, Alexander Ebenbichler, Christoph Gstraunthaler, Gerhard Salzmann, Karin Bakry, Rania Niederwanger, Andreas Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells |
title | Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells |
title_full | Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells |
title_fullStr | Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells |
title_full_unstemmed | Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells |
title_short | Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells |
title_sort | serotonin improves glucose metabolism by serotonylation of the small gtpase rab4 in l6 skeletal muscle cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209910/ https://www.ncbi.nlm.nih.gov/pubmed/28053672 http://dx.doi.org/10.1186/s13098-016-0201-1 |
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