Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2)

Autores
Leiss, Veronika; Flockerzie, Katarina; Novakovic, Ana; Rath, Michaela; Schönsiegel, Annika; Birnbaumer, Lutz; Schürmann, Annette; Harteneck, Christian; Nürnberg, Bernd
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Bordetella pertussis toxin (PTx), also known as islet-activating protein, induces insulin secretion by ADP-ribosylation of inhibitory G proteins. PTx-induced insulin secretion may result either from inactivation of Gα(o) proteins or from combined inactivation of Gα(o), Gα(i1), Gα(i2), and Gα(i3) isoforms. However, the specific role of Gα(i2) in pancreatic β-cells still remains unknown. In global (Gα(i2)(-/-)) and β-cell-specific (Gα(i2)(βcko)) gene-targeted Gα(i2) mouse models, we studied glucose homeostasis and islet functions. Insulin secretion experiments and intracellular Ca²⁺ measurements were used to characterize Gα(i2) function in vitro. Gα(i2)(-/-) and Gα(i2)(βcko) mice showed an unexpected metabolic phenotype, i.e., significantly lower plasma insulin levels upon intraperitoneal glucose challenge in Gα(i2)(-/-) and Gα(i2)(βcko) mice, whereas plasma glucose concentrations were unchanged in Gα(i2)(-/-) but significantly increased in Gα(i2)(βcko) mice. These findings indicate a novel albeit unexpected role for Gα(i2) in the expression, turnover, and/or release of insulin from islets. Detection of insulin secretion in isolated islets did not show differences in response to high (16 mM) glucose concentrations between control and β-cell-specific Gα(i2)-deficient mice. In contrast, the two- to threefold increase in insulin secretion evoked by L-arginine or L-ornithine (in the presence of 16 mM glucose) was significantly reduced in islets lacking Gα(i2). In accord with a reduced level of insulin secretion, intracellular calcium concentrations induced by the agonistic amino acid L-arginine did not reach control levels in β-cells. The presented analysis of gene-targeted mice provides novel insights in the role of β-cell Gα(i2) showing that amino acid-induced insulin-release depends on Gα(i2).
Fil: Leiss, Veronika. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Flockerzie, Katarina. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Novakovic, Ana. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Rath, Michaela. German Institute of Human Nutrition. Department of Experimental Diabetology; Alemania
Fil: Schönsiegel, Annika. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Birnbaumer, Lutz. National Institute ofEnvironmental Health Sciences. Laboratory of Neurobiology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schürmann, Annette. German Institute of Human Nutrition. Department of Experimental Diabetology; Alemania
Fil: Harteneck, Christian. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Nürnberg, Bernd. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
Materia
PROTEINA G(i2)
INSULIN DOSING
GPCR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/98903
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/98903
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2)Leiss, VeronikaFlockerzie, KatarinaNovakovic, AnaRath, MichaelaSchönsiegel, AnnikaBirnbaumer, LutzSchürmann, AnnetteHarteneck, ChristianNürnberg, BerndPROTEINA G(i2)INSULIN DOSINGGPCRhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Bordetella pertussis toxin (PTx), also known as islet-activating protein, induces insulin secretion by ADP-ribosylation of inhibitory G proteins. PTx-induced insulin secretion may result either from inactivation of Gα(o) proteins or from combined inactivation of Gα(o), Gα(i1), Gα(i2), and Gα(i3) isoforms. However, the specific role of Gα(i2) in pancreatic β-cells still remains unknown. In global (Gα(i2)(-/-)) and β-cell-specific (Gα(i2)(βcko)) gene-targeted Gα(i2) mouse models, we studied glucose homeostasis and islet functions. Insulin secretion experiments and intracellular Ca²⁺ measurements were used to characterize Gα(i2) function in vitro. Gα(i2)(-/-) and Gα(i2)(βcko) mice showed an unexpected metabolic phenotype, i.e., significantly lower plasma insulin levels upon intraperitoneal glucose challenge in Gα(i2)(-/-) and Gα(i2)(βcko) mice, whereas plasma glucose concentrations were unchanged in Gα(i2)(-/-) but significantly increased in Gα(i2)(βcko) mice. These findings indicate a novel albeit unexpected role for Gα(i2) in the expression, turnover, and/or release of insulin from islets. Detection of insulin secretion in isolated islets did not show differences in response to high (16 mM) glucose concentrations between control and β-cell-specific Gα(i2)-deficient mice. In contrast, the two- to threefold increase in insulin secretion evoked by L-arginine or L-ornithine (in the presence of 16 mM glucose) was significantly reduced in islets lacking Gα(i2). In accord with a reduced level of insulin secretion, intracellular calcium concentrations induced by the agonistic amino acid L-arginine did not reach control levels in β-cells. The presented analysis of gene-targeted mice provides novel insights in the role of β-cell Gα(i2) showing that amino acid-induced insulin-release depends on Gα(i2).Fil: Leiss, Veronika. University of Tübingen. Department of Pharmacology and Experimental Therapy; AlemaniaFil: Flockerzie, Katarina. University of Tübingen. Department of Pharmacology and Experimental Therapy; AlemaniaFil: Novakovic, Ana. University of Tübingen. Department of Pharmacology and Experimental Therapy; AlemaniaFil: Rath, Michaela. German Institute of Human Nutrition. Department of Experimental Diabetology; AlemaniaFil: Schönsiegel, Annika. University of Tübingen. Department of Pharmacology and Experimental Therapy; AlemaniaFil: Birnbaumer, Lutz. National Institute ofEnvironmental Health Sciences. Laboratory of Neurobiology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schürmann, Annette. German Institute of Human Nutrition. Department of Experimental Diabetology; AlemaniaFil: Harteneck, Christian. University of Tübingen. Department of Pharmacology and Experimental Therapy; AlemaniaFil: Nürnberg, Bernd. University of Tübingen. Department of Pharmacology and Experimental Therapy; AlemaniaAmerican Physiological Society2014-11-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/mswordapplication/pdfhttp://hdl.handle.net/11336/98903Leiss, Veronika; Flockerzie, Katarina; Novakovic, Ana; Rath, Michaela; Schönsiegel, Annika; et al.; Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2); American Physiological Society; American Journal of Physiology - Endocrinology and Metabolism; 307; 1-11-2014; E800–E8120193-1849CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.physiology.org/doi/full/10.1152/ajpendo.00337.2014info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpendo.00337.2014info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:09:46Zoai:ri.conicet.gov.ar:11336/98903instacron: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:34982025-09-03 10:09:47.015CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2)
title Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2)
spellingShingle Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2)
Leiss, Veronika
PROTEINA G(i2)
INSULIN DOSING
GPCR
title_short Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2)
title_full Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2)
title_fullStr Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2)
title_full_unstemmed Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2)
title_sort Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2)
dc.creator.none.fl_str_mv Leiss, Veronika
Flockerzie, Katarina
Novakovic, Ana
Rath, Michaela
Schönsiegel, Annika
Birnbaumer, Lutz
Schürmann, Annette
Harteneck, Christian
Nürnberg, Bernd
author Leiss, Veronika
author_facet Leiss, Veronika
Flockerzie, Katarina
Novakovic, Ana
Rath, Michaela
Schönsiegel, Annika
Birnbaumer, Lutz
Schürmann, Annette
Harteneck, Christian
Nürnberg, Bernd
author_role author
author2 Flockerzie, Katarina
Novakovic, Ana
Rath, Michaela
Schönsiegel, Annika
Birnbaumer, Lutz
Schürmann, Annette
Harteneck, Christian
Nürnberg, Bernd
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PROTEINA G(i2)
INSULIN DOSING
GPCR
topic PROTEINA G(i2)
INSULIN DOSING
GPCR
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Bordetella pertussis toxin (PTx), also known as islet-activating protein, induces insulin secretion by ADP-ribosylation of inhibitory G proteins. PTx-induced insulin secretion may result either from inactivation of Gα(o) proteins or from combined inactivation of Gα(o), Gα(i1), Gα(i2), and Gα(i3) isoforms. However, the specific role of Gα(i2) in pancreatic β-cells still remains unknown. In global (Gα(i2)(-/-)) and β-cell-specific (Gα(i2)(βcko)) gene-targeted Gα(i2) mouse models, we studied glucose homeostasis and islet functions. Insulin secretion experiments and intracellular Ca²⁺ measurements were used to characterize Gα(i2) function in vitro. Gα(i2)(-/-) and Gα(i2)(βcko) mice showed an unexpected metabolic phenotype, i.e., significantly lower plasma insulin levels upon intraperitoneal glucose challenge in Gα(i2)(-/-) and Gα(i2)(βcko) mice, whereas plasma glucose concentrations were unchanged in Gα(i2)(-/-) but significantly increased in Gα(i2)(βcko) mice. These findings indicate a novel albeit unexpected role for Gα(i2) in the expression, turnover, and/or release of insulin from islets. Detection of insulin secretion in isolated islets did not show differences in response to high (16 mM) glucose concentrations between control and β-cell-specific Gα(i2)-deficient mice. In contrast, the two- to threefold increase in insulin secretion evoked by L-arginine or L-ornithine (in the presence of 16 mM glucose) was significantly reduced in islets lacking Gα(i2). In accord with a reduced level of insulin secretion, intracellular calcium concentrations induced by the agonistic amino acid L-arginine did not reach control levels in β-cells. The presented analysis of gene-targeted mice provides novel insights in the role of β-cell Gα(i2) showing that amino acid-induced insulin-release depends on Gα(i2).
Fil: Leiss, Veronika. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Flockerzie, Katarina. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Novakovic, Ana. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Rath, Michaela. German Institute of Human Nutrition. Department of Experimental Diabetology; Alemania
Fil: Schönsiegel, Annika. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Birnbaumer, Lutz. National Institute ofEnvironmental Health Sciences. Laboratory of Neurobiology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schürmann, Annette. German Institute of Human Nutrition. Department of Experimental Diabetology; Alemania
Fil: Harteneck, Christian. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Nürnberg, Bernd. University of Tübingen. Department of Pharmacology and Experimental Therapy; Alemania
description Bordetella pertussis toxin (PTx), also known as islet-activating protein, induces insulin secretion by ADP-ribosylation of inhibitory G proteins. PTx-induced insulin secretion may result either from inactivation of Gα(o) proteins or from combined inactivation of Gα(o), Gα(i1), Gα(i2), and Gα(i3) isoforms. However, the specific role of Gα(i2) in pancreatic β-cells still remains unknown. In global (Gα(i2)(-/-)) and β-cell-specific (Gα(i2)(βcko)) gene-targeted Gα(i2) mouse models, we studied glucose homeostasis and islet functions. Insulin secretion experiments and intracellular Ca²⁺ measurements were used to characterize Gα(i2) function in vitro. Gα(i2)(-/-) and Gα(i2)(βcko) mice showed an unexpected metabolic phenotype, i.e., significantly lower plasma insulin levels upon intraperitoneal glucose challenge in Gα(i2)(-/-) and Gα(i2)(βcko) mice, whereas plasma glucose concentrations were unchanged in Gα(i2)(-/-) but significantly increased in Gα(i2)(βcko) mice. These findings indicate a novel albeit unexpected role for Gα(i2) in the expression, turnover, and/or release of insulin from islets. Detection of insulin secretion in isolated islets did not show differences in response to high (16 mM) glucose concentrations between control and β-cell-specific Gα(i2)-deficient mice. In contrast, the two- to threefold increase in insulin secretion evoked by L-arginine or L-ornithine (in the presence of 16 mM glucose) was significantly reduced in islets lacking Gα(i2). In accord with a reduced level of insulin secretion, intracellular calcium concentrations induced by the agonistic amino acid L-arginine did not reach control levels in β-cells. The presented analysis of gene-targeted mice provides novel insights in the role of β-cell Gα(i2) showing that amino acid-induced insulin-release depends on Gα(i2).
publishDate 2014
dc.date.none.fl_str_mv 2014-11-01
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/11336/98903
Leiss, Veronika; Flockerzie, Katarina; Novakovic, Ana; Rath, Michaela; Schönsiegel, Annika; et al.; Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2); American Physiological Society; American Journal of Physiology - Endocrinology and Metabolism; 307; 1-11-2014; E800–E812
0193-1849
CONICET Digital
CONICET
url http://hdl.handle.net/11336/98903
identifier_str_mv Leiss, Veronika; Flockerzie, Katarina; Novakovic, Ana; Rath, Michaela; Schönsiegel, Annika; et al.; Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2); American Physiological Society; American Journal of Physiology - Endocrinology and Metabolism; 307; 1-11-2014; E800–E812
0193-1849
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://journals.physiology.org/doi/full/10.1152/ajpendo.00337.2014
info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpendo.00337.2014
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/msword
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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 13.13397

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