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An insulin-regulated arrestin domain protein controls hepatic glucagon action
Glucagon signaling is essential for maintaining normoglycemia in mammals. The arrestin fold superfamily of proteins controls the trafficking, turnover, and signaling of transmembrane receptors as well as other intracellular signaling functions. Further investigation is needed to understand the in vi...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413355/ https://www.ncbi.nlm.nih.gov/pubmed/37451484 http://dx.doi.org/10.1016/j.jbc.2023.105045 |
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author | Dagdeviren, Sezin Hoang, Megan F. Sarikhani, Mohsen Meier, Vanessa Benoit, Jake C. Okawa, Marinna C. Melnik, Veronika Y. Ricci-Blair, Elisabeth M. Foot, Natalie Friedline, Randall H. Hu, Xiaodi Tauer, Lauren A. Srinivasan, Arvind Prigozhin, Maxim B. Shenoy, Sudha K. Kumar, Sharad Kim, Jason K. Lee, Richard T. |
author_facet | Dagdeviren, Sezin Hoang, Megan F. Sarikhani, Mohsen Meier, Vanessa Benoit, Jake C. Okawa, Marinna C. Melnik, Veronika Y. Ricci-Blair, Elisabeth M. Foot, Natalie Friedline, Randall H. Hu, Xiaodi Tauer, Lauren A. Srinivasan, Arvind Prigozhin, Maxim B. Shenoy, Sudha K. Kumar, Sharad Kim, Jason K. Lee, Richard T. |
author_sort | Dagdeviren, Sezin |
collection | PubMed |
description | Glucagon signaling is essential for maintaining normoglycemia in mammals. The arrestin fold superfamily of proteins controls the trafficking, turnover, and signaling of transmembrane receptors as well as other intracellular signaling functions. Further investigation is needed to understand the in vivo functions of the arrestin domain–containing 4 (ARRDC4) protein family member and whether it is involved in mammalian glucose metabolism. Here, we show that mice with a global deletion of the ARRDC4 protein have impaired glucagon responses and gluconeogenesis at a systemic and molecular level. Mice lacking ARRDC4 exhibited lower glucose levels after fasting and could not suppress gluconeogenesis at the refed state. We also show that ARRDC4 coimmunoprecipitates with the glucagon receptor, and ARRDC4 expression is suppressed by insulin. These results define ARRDC4 as a critical regulator of glucagon signaling and glucose homeostasis and reveal a novel intersection of insulin and glucagon pathways in the liver. |
format | Online Article Text |
id | pubmed-10413355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-104133552023-08-11 An insulin-regulated arrestin domain protein controls hepatic glucagon action Dagdeviren, Sezin Hoang, Megan F. Sarikhani, Mohsen Meier, Vanessa Benoit, Jake C. Okawa, Marinna C. Melnik, Veronika Y. Ricci-Blair, Elisabeth M. Foot, Natalie Friedline, Randall H. Hu, Xiaodi Tauer, Lauren A. Srinivasan, Arvind Prigozhin, Maxim B. Shenoy, Sudha K. Kumar, Sharad Kim, Jason K. Lee, Richard T. J Biol Chem Research Article Glucagon signaling is essential for maintaining normoglycemia in mammals. The arrestin fold superfamily of proteins controls the trafficking, turnover, and signaling of transmembrane receptors as well as other intracellular signaling functions. Further investigation is needed to understand the in vivo functions of the arrestin domain–containing 4 (ARRDC4) protein family member and whether it is involved in mammalian glucose metabolism. Here, we show that mice with a global deletion of the ARRDC4 protein have impaired glucagon responses and gluconeogenesis at a systemic and molecular level. Mice lacking ARRDC4 exhibited lower glucose levels after fasting and could not suppress gluconeogenesis at the refed state. We also show that ARRDC4 coimmunoprecipitates with the glucagon receptor, and ARRDC4 expression is suppressed by insulin. These results define ARRDC4 as a critical regulator of glucagon signaling and glucose homeostasis and reveal a novel intersection of insulin and glucagon pathways in the liver. American Society for Biochemistry and Molecular Biology 2023-07-13 /pmc/articles/PMC10413355/ /pubmed/37451484 http://dx.doi.org/10.1016/j.jbc.2023.105045 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Dagdeviren, Sezin Hoang, Megan F. Sarikhani, Mohsen Meier, Vanessa Benoit, Jake C. Okawa, Marinna C. Melnik, Veronika Y. Ricci-Blair, Elisabeth M. Foot, Natalie Friedline, Randall H. Hu, Xiaodi Tauer, Lauren A. Srinivasan, Arvind Prigozhin, Maxim B. Shenoy, Sudha K. Kumar, Sharad Kim, Jason K. Lee, Richard T. An insulin-regulated arrestin domain protein controls hepatic glucagon action |
title | An insulin-regulated arrestin domain protein controls hepatic glucagon action |
title_full | An insulin-regulated arrestin domain protein controls hepatic glucagon action |
title_fullStr | An insulin-regulated arrestin domain protein controls hepatic glucagon action |
title_full_unstemmed | An insulin-regulated arrestin domain protein controls hepatic glucagon action |
title_short | An insulin-regulated arrestin domain protein controls hepatic glucagon action |
title_sort | insulin-regulated arrestin domain protein controls hepatic glucagon action |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413355/ https://www.ncbi.nlm.nih.gov/pubmed/37451484 http://dx.doi.org/10.1016/j.jbc.2023.105045 |
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