SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes

Pancreatic β cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here, we report that succinate receptor 1 (SUCNR1) is expressed in β cells and is upregulated in hyperglycemic states in mice and humans. We found that succinate acted as a hor...

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Autores: Sabadell-Basallote, Joan, Astiarraga, Brenno, Castaño, Carlos, Ejarque, Miriam, Repollés de Dalmau, Maria, Quesada, Ivan, Blanco, Jordi, Núñez-Roa, Catalina, Rodríguez-Peña, M., Martínez, Laia, F De Jesus, Dario, Marroqui Esclapez, Laura, Bosch, Ramon, Montanya, Eduard, Sureda, Francesc, Tura, Andrea, Mari, Andrea, Kulkarni, Rohit N., Vendrell, Joan, Fernández-Veledo, Sonia
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Miguel Hernández de Elche
Repositorio:REDIUMH. Depósito Digital de la UMH
OAI Identifier:oai:dspace.umh.es:11000/38552
Acceso en línea:https://hdl.handle.net/11000/38552
Access Level:acceso abierto
Palabra clave:CDU::6 - Ciencias aplicadas::61 - Medicina::612 - Fisiología
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spelling SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetesSabadell-Basallote, JoanAstiarraga, BrennoCastaño, CarlosEjarque, MiriamRepollés de Dalmau, MariaQuesada, IvanBlanco, JordiNúñez-Roa, CatalinaRodríguez-Peña, M.Martínez, LaiaF De Jesus, DarioMarroqui Esclapez, LauraBosch, RamonMontanya, EduardSureda, FrancescTura, AndreaMari, AndreaKulkarni, Rohit N.Vendrell, JoanFernández-Veledo, SoniaCDU::6 - Ciencias aplicadas::61 - Medicina::612 - FisiologíaPancreatic β cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here, we report that succinate receptor 1 (SUCNR1) is expressed in β cells and is upregulated in hyperglycemic states in mice and humans. We found that succinate acted as a hormone-like metabolite and stimulated insulin secretion via a SUCNR1-Gq-PKC–dependent mechanism in human β cells. Mice with β cell–specific Sucnr1 deficiency exhibited impaired glucose tolerance and insulin secretion on a high-fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet-induced insulin resistance. Patients with impaired glucose tolerance showed an enhanced nutrition-related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states.American Society for Clinical InvestigationDepartamentos de la UMH::Fisiología202520252024info:eu-repo/semantics/articleapplication/pdf16application/pdfhttps://hdl.handle.net/11000/38552reponame:REDIUMH. Depósito Digital de la UMHinstname:Universidad Miguel Hernández de ElcheInglés13412https://doi.org/10.1172/JCI173214info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:dspace.umh.es:11000/385522026-05-27T13:36:21Z
dc.title.none.fl_str_mv SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes
title SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes
spellingShingle SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes
Sabadell-Basallote, Joan
CDU::6 - Ciencias aplicadas::61 - Medicina::612 - Fisiología
title_short SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes
title_full SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes
title_fullStr SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes
title_full_unstemmed SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes
title_sort SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes
dc.creator.none.fl_str_mv Sabadell-Basallote, Joan
Astiarraga, Brenno
Castaño, Carlos
Ejarque, Miriam
Repollés de Dalmau, Maria
Quesada, Ivan
Blanco, Jordi
Núñez-Roa, Catalina
Rodríguez-Peña, M.
Martínez, Laia
F De Jesus, Dario
Marroqui Esclapez, Laura
Bosch, Ramon
Montanya, Eduard
Sureda, Francesc
Tura, Andrea
Mari, Andrea
Kulkarni, Rohit N.
Vendrell, Joan
Fernández-Veledo, Sonia
author Sabadell-Basallote, Joan
author_facet Sabadell-Basallote, Joan
Astiarraga, Brenno
Castaño, Carlos
Ejarque, Miriam
Repollés de Dalmau, Maria
Quesada, Ivan
Blanco, Jordi
Núñez-Roa, Catalina
Rodríguez-Peña, M.
Martínez, Laia
F De Jesus, Dario
Marroqui Esclapez, Laura
Bosch, Ramon
Montanya, Eduard
Sureda, Francesc
Tura, Andrea
Mari, Andrea
Kulkarni, Rohit N.
Vendrell, Joan
Fernández-Veledo, Sonia
author_role author
author2 Astiarraga, Brenno
Castaño, Carlos
Ejarque, Miriam
Repollés de Dalmau, Maria
Quesada, Ivan
Blanco, Jordi
Núñez-Roa, Catalina
Rodríguez-Peña, M.
Martínez, Laia
F De Jesus, Dario
Marroqui Esclapez, Laura
Bosch, Ramon
Montanya, Eduard
Sureda, Francesc
Tura, Andrea
Mari, Andrea
Kulkarni, Rohit N.
Vendrell, Joan
Fernández-Veledo, Sonia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamentos de la UMH::Fisiología
dc.subject.none.fl_str_mv CDU::6 - Ciencias aplicadas::61 - Medicina::612 - Fisiología
topic CDU::6 - Ciencias aplicadas::61 - Medicina::612 - Fisiología
description Pancreatic β cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here, we report that succinate receptor 1 (SUCNR1) is expressed in β cells and is upregulated in hyperglycemic states in mice and humans. We found that succinate acted as a hormone-like metabolite and stimulated insulin secretion via a SUCNR1-Gq-PKC–dependent mechanism in human β cells. Mice with β cell–specific Sucnr1 deficiency exhibited impaired glucose tolerance and insulin secretion on a high-fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet-induced insulin resistance. Patients with impaired glucose tolerance showed an enhanced nutrition-related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/11000/38552
url https://hdl.handle.net/11000/38552
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv 134
12
https://doi.org/10.1172/JCI173214
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.format.none.fl_str_mv application/pdf
16
application/pdf
dc.publisher.none.fl_str_mv American Society for Clinical Investigation
publisher.none.fl_str_mv American Society for Clinical Investigation
dc.source.none.fl_str_mv reponame:REDIUMH. Depósito Digital de la UMH
instname:Universidad Miguel Hernández de Elche
instname_str Universidad Miguel Hernández de Elche
reponame_str REDIUMH. Depósito Digital de la UMH
collection REDIUMH. Depósito Digital de la UMH
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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