TRPC3 Regulates Islet Beta‐Cell Insulin Secretion

Autores
Rached, Gaëlle; Saliba, Youakim; Maddah, Dina; Hajal, Joelle; Smayra, Viviane; Bakhos, Jules Joel; Groschner, Klaus; Birnbaumer, Lutz; Fares, Nassim
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Insulin release is tightly controlled by glucose-stimulated calcium (GSCa) through hitherto equivocal pathways. This study investigates TRPC3, a non-selective cation channel, as a critical regulator of insulin secretion and glucose control. TRPC3´s involvement in glucose-stimulated insulin secretion (GSIS) is studied in human and animal islets. TRPC3-dependent in vivo insulin secretion is investigated using pharmacological tools and Trpc3-/- mice. TRPC3´s involvement in islet glucose uptake and GSCa is explored using fluorescent glucose analogue 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose and calcium imaging. TRPC3 modulation by a small-molecule activator, GSK1702934A, is evaluated in type 2 diabetic mice. TRPC3 is functionally expressed in human and mouse islet beta cells. TRPC3-controlled insulin secretion is KATP -independent and primarily mediated by diacylglycerol channel regulation of the cytosolic calcium oscillations following glucose stimulation. Conversely, glucose uptake in islets is independent of TRPC3. TRPC3 pharmacologic inhibition and knockout in mice lead to defective insulin secretion and glucose intolerance. Subsequently, TRPC3 activation through targeted small-molecule enhances insulin secretion and alleviates diabetes hallmarks in animals. This study imputes a function for TRPC3 at the onset of GSIS. These insights strengthen one´s knowledge of insulin secretion physiology and set forth the TRPC3 channel as an appealing candidate for drug development in the treatment of diabetes.
Fil: Rached, Gaëlle. Saint Joseph University Of Beirut; Líbano
Fil: Saliba, Youakim. Saint Joseph University Of Beirut; Líbano
Fil: Maddah, Dina. Saint Joseph University Of Beirut; Líbano
Fil: Hajal, Joelle. Saint Joseph University Of Beirut; Líbano
Fil: Smayra, Viviane. Saint Joseph University Of Beirut; Líbano
Fil: Bakhos, Jules Joel. Saint Joseph University Of Beirut; Líbano
Fil: Groschner, Klaus. University of Graz; Austria
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Fares, Nassim. Saint Joseph University Of Beirut; Líbano
Materia
TRPC3
CALCIUM
INSULIN
GSIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/256173
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/256173
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TRPC3 Regulates Islet Beta‐Cell Insulin SecretionRached, GaëlleSaliba, YouakimMaddah, DinaHajal, JoelleSmayra, VivianeBakhos, Jules JoelGroschner, KlausBirnbaumer, LutzFares, NassimTRPC3CALCIUMINSULINGSIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Insulin release is tightly controlled by glucose-stimulated calcium (GSCa) through hitherto equivocal pathways. This study investigates TRPC3, a non-selective cation channel, as a critical regulator of insulin secretion and glucose control. TRPC3´s involvement in glucose-stimulated insulin secretion (GSIS) is studied in human and animal islets. TRPC3-dependent in vivo insulin secretion is investigated using pharmacological tools and Trpc3-/- mice. TRPC3´s involvement in islet glucose uptake and GSCa is explored using fluorescent glucose analogue 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose and calcium imaging. TRPC3 modulation by a small-molecule activator, GSK1702934A, is evaluated in type 2 diabetic mice. TRPC3 is functionally expressed in human and mouse islet beta cells. TRPC3-controlled insulin secretion is KATP -independent and primarily mediated by diacylglycerol channel regulation of the cytosolic calcium oscillations following glucose stimulation. Conversely, glucose uptake in islets is independent of TRPC3. TRPC3 pharmacologic inhibition and knockout in mice lead to defective insulin secretion and glucose intolerance. Subsequently, TRPC3 activation through targeted small-molecule enhances insulin secretion and alleviates diabetes hallmarks in animals. This study imputes a function for TRPC3 at the onset of GSIS. These insights strengthen one´s knowledge of insulin secretion physiology and set forth the TRPC3 channel as an appealing candidate for drug development in the treatment of diabetes.Fil: Rached, Gaëlle. Saint Joseph University Of Beirut; LíbanoFil: Saliba, Youakim. Saint Joseph University Of Beirut; LíbanoFil: Maddah, Dina. Saint Joseph University Of Beirut; LíbanoFil: Hajal, Joelle. Saint Joseph University Of Beirut; LíbanoFil: Smayra, Viviane. Saint Joseph University Of Beirut; LíbanoFil: Bakhos, Jules Joel. Saint Joseph University Of Beirut; LíbanoFil: Groschner, Klaus. University of Graz; AustriaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. National Institute of Environmental Health Sciences; Estados UnidosFil: Fares, Nassim. Saint Joseph University Of Beirut; LíbanoWiley2023-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/256173Rached, Gaëlle; Saliba, Youakim; Maddah, Dina; Hajal, Joelle; Smayra, Viviane; et al.; TRPC3 Regulates Islet Beta‐Cell Insulin Secretion; Wiley; Advanced Science; 10; 6; 1-2023; 1-172198-3844CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/advs.202204846info:eu-repo/semantics/altIdentifier/doi/10.1002/advs.202204846info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:06:35Zoai:ri.conicet.gov.ar:11336/256173instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:06:36.054CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TRPC3 Regulates Islet Beta‐Cell Insulin Secretion
title TRPC3 Regulates Islet Beta‐Cell Insulin Secretion
spellingShingle TRPC3 Regulates Islet Beta‐Cell Insulin Secretion
Rached, Gaëlle
TRPC3
CALCIUM
INSULIN
GSIS
title_short TRPC3 Regulates Islet Beta‐Cell Insulin Secretion
title_full TRPC3 Regulates Islet Beta‐Cell Insulin Secretion
title_fullStr TRPC3 Regulates Islet Beta‐Cell Insulin Secretion
title_full_unstemmed TRPC3 Regulates Islet Beta‐Cell Insulin Secretion
title_sort TRPC3 Regulates Islet Beta‐Cell Insulin Secretion
dc.creator.none.fl_str_mv Rached, Gaëlle
Saliba, Youakim
Maddah, Dina
Hajal, Joelle
Smayra, Viviane
Bakhos, Jules Joel
Groschner, Klaus
Birnbaumer, Lutz
Fares, Nassim
author Rached, Gaëlle
author_facet Rached, Gaëlle
Saliba, Youakim
Maddah, Dina
Hajal, Joelle
Smayra, Viviane
Bakhos, Jules Joel
Groschner, Klaus
Birnbaumer, Lutz
Fares, Nassim
author_role author
author2 Saliba, Youakim
Maddah, Dina
Hajal, Joelle
Smayra, Viviane
Bakhos, Jules Joel
Groschner, Klaus
Birnbaumer, Lutz
Fares, Nassim
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TRPC3
CALCIUM
INSULIN
GSIS
topic TRPC3
CALCIUM
INSULIN
GSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Insulin release is tightly controlled by glucose-stimulated calcium (GSCa) through hitherto equivocal pathways. This study investigates TRPC3, a non-selective cation channel, as a critical regulator of insulin secretion and glucose control. TRPC3´s involvement in glucose-stimulated insulin secretion (GSIS) is studied in human and animal islets. TRPC3-dependent in vivo insulin secretion is investigated using pharmacological tools and Trpc3-/- mice. TRPC3´s involvement in islet glucose uptake and GSCa is explored using fluorescent glucose analogue 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose and calcium imaging. TRPC3 modulation by a small-molecule activator, GSK1702934A, is evaluated in type 2 diabetic mice. TRPC3 is functionally expressed in human and mouse islet beta cells. TRPC3-controlled insulin secretion is KATP -independent and primarily mediated by diacylglycerol channel regulation of the cytosolic calcium oscillations following glucose stimulation. Conversely, glucose uptake in islets is independent of TRPC3. TRPC3 pharmacologic inhibition and knockout in mice lead to defective insulin secretion and glucose intolerance. Subsequently, TRPC3 activation through targeted small-molecule enhances insulin secretion and alleviates diabetes hallmarks in animals. This study imputes a function for TRPC3 at the onset of GSIS. These insights strengthen one´s knowledge of insulin secretion physiology and set forth the TRPC3 channel as an appealing candidate for drug development in the treatment of diabetes.
Fil: Rached, Gaëlle. Saint Joseph University Of Beirut; Líbano
Fil: Saliba, Youakim. Saint Joseph University Of Beirut; Líbano
Fil: Maddah, Dina. Saint Joseph University Of Beirut; Líbano
Fil: Hajal, Joelle. Saint Joseph University Of Beirut; Líbano
Fil: Smayra, Viviane. Saint Joseph University Of Beirut; Líbano
Fil: Bakhos, Jules Joel. Saint Joseph University Of Beirut; Líbano
Fil: Groschner, Klaus. University of Graz; Austria
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Fares, Nassim. Saint Joseph University Of Beirut; Líbano
description Insulin release is tightly controlled by glucose-stimulated calcium (GSCa) through hitherto equivocal pathways. This study investigates TRPC3, a non-selective cation channel, as a critical regulator of insulin secretion and glucose control. TRPC3´s involvement in glucose-stimulated insulin secretion (GSIS) is studied in human and animal islets. TRPC3-dependent in vivo insulin secretion is investigated using pharmacological tools and Trpc3-/- mice. TRPC3´s involvement in islet glucose uptake and GSCa is explored using fluorescent glucose analogue 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose and calcium imaging. TRPC3 modulation by a small-molecule activator, GSK1702934A, is evaluated in type 2 diabetic mice. TRPC3 is functionally expressed in human and mouse islet beta cells. TRPC3-controlled insulin secretion is KATP -independent and primarily mediated by diacylglycerol channel regulation of the cytosolic calcium oscillations following glucose stimulation. Conversely, glucose uptake in islets is independent of TRPC3. TRPC3 pharmacologic inhibition and knockout in mice lead to defective insulin secretion and glucose intolerance. Subsequently, TRPC3 activation through targeted small-molecule enhances insulin secretion and alleviates diabetes hallmarks in animals. This study imputes a function for TRPC3 at the onset of GSIS. These insights strengthen one´s knowledge of insulin secretion physiology and set forth the TRPC3 channel as an appealing candidate for drug development in the treatment of diabetes.
publishDate 2023
dc.date.none.fl_str_mv 2023-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/256173
Rached, Gaëlle; Saliba, Youakim; Maddah, Dina; Hajal, Joelle; Smayra, Viviane; et al.; TRPC3 Regulates Islet Beta‐Cell Insulin Secretion; Wiley; Advanced Science; 10; 6; 1-2023; 1-17
2198-3844
CONICET Digital
CONICET
url http://hdl.handle.net/11336/256173
identifier_str_mv Rached, Gaëlle; Saliba, Youakim; Maddah, Dina; Hajal, Joelle; Smayra, Viviane; et al.; TRPC3 Regulates Islet Beta‐Cell Insulin Secretion; Wiley; Advanced Science; 10; 6; 1-2023; 1-17
2198-3844
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/advs.202204846
info:eu-repo/semantics/altIdentifier/doi/10.1002/advs.202204846
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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