Ghrelin directly stimulates glucagon secretion from pancreatic α-cells

Autores
Chuang, Jen Chieh; Sakata, Ichiro; Kohno, Dasuke; Perello, Mario; Lawrence, Serri Osborne; Repa, Joyce R.; Zigman, Jeffrey M
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Previous work has demonstrated that the peptide hormone ghrelin raises blood glucose. Such has been attributed to ghrelin's ability to enhance GH secretion, restrict insulin release, and/or reduce insulin sensitivity. Ghrelin's reported effects on glucagon have been inconsistent. Here, both animal- and cell-based systems were used to determine the role of glucagon in mediating ghrelin's effects on blood glucose. The tissue and cell distribution of ghrelin receptors (GHSR) was evaluated by quantitative PCR and histochemistry. Plasma glucagon levels were determined following acute acyl-ghrelin injections and in pharmacological and/or transgenic mouse models of ghrelin overexpression and GHSR deletion. Isolated mouse islets and the α-cell lines αTC1 and InR1G9 were used to evaluate ghrelin's effects on glucagon secretion and the role of calcium and ERK in this activity. GHSR mRNA was abundantly expressed in mouse islets and colocalized with glucagon in α-cells. Elevation of acyl-ghrelin acutely (after sc administration, such that physiologically relevant plasma ghrelin levels were achieved) and chronically (by slow-releasing osmotic pumps and as observed in transgenic mice harboring ghrelinomas) led to higher plasma glucagon and increased blood glucose. Conversely, genetic GHSR deletion was associated with lower plasma glucagon and reduced fasting blood glucose. Acyl-ghrelin increased glucagon secretion in a dosedependent manner from mouse islets and α-cell lines, in a manner requiring elevation of intracellular calcium and phosphorylation of ERK. Our study shows that ghrelin's regulation of blood glucose involves direct stimulation of glucagon secretion from α-cells and introduces the ghrelin-glucagon axis as an important mechanism controlling glycemia under fasting conditions.
Fil: Chuang, Jen Chieh. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Sakata, Ichiro. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Kohno, Dasuke. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Perello, Mario. University of Texas. Southwestern Medical Center; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Lawrence, Serri Osborne. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Repa, Joyce R.. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Zigman, Jeffrey M. University of Texas. Southwestern Medical Center; Estados Unidos
Materia
LEPTINA
GHRELINA
PEPTIDE HORMONE
GLUCAGON
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:11336/85915
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/85915
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ghrelin directly stimulates glucagon secretion from pancreatic α-cellsChuang, Jen ChiehSakata, IchiroKohno, DasukePerello, MarioLawrence, Serri OsborneRepa, Joyce R.Zigman, Jeffrey MLEPTINAGHRELINAPEPTIDE HORMONEGLUCAGONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Previous work has demonstrated that the peptide hormone ghrelin raises blood glucose. Such has been attributed to ghrelin's ability to enhance GH secretion, restrict insulin release, and/or reduce insulin sensitivity. Ghrelin's reported effects on glucagon have been inconsistent. Here, both animal- and cell-based systems were used to determine the role of glucagon in mediating ghrelin's effects on blood glucose. The tissue and cell distribution of ghrelin receptors (GHSR) was evaluated by quantitative PCR and histochemistry. Plasma glucagon levels were determined following acute acyl-ghrelin injections and in pharmacological and/or transgenic mouse models of ghrelin overexpression and GHSR deletion. Isolated mouse islets and the α-cell lines αTC1 and InR1G9 were used to evaluate ghrelin's effects on glucagon secretion and the role of calcium and ERK in this activity. GHSR mRNA was abundantly expressed in mouse islets and colocalized with glucagon in α-cells. Elevation of acyl-ghrelin acutely (after sc administration, such that physiologically relevant plasma ghrelin levels were achieved) and chronically (by slow-releasing osmotic pumps and as observed in transgenic mice harboring ghrelinomas) led to higher plasma glucagon and increased blood glucose. Conversely, genetic GHSR deletion was associated with lower plasma glucagon and reduced fasting blood glucose. Acyl-ghrelin increased glucagon secretion in a dosedependent manner from mouse islets and α-cell lines, in a manner requiring elevation of intracellular calcium and phosphorylation of ERK. Our study shows that ghrelin's regulation of blood glucose involves direct stimulation of glucagon secretion from α-cells and introduces the ghrelin-glucagon axis as an important mechanism controlling glycemia under fasting conditions.Fil: Chuang, Jen Chieh. University of Texas. Southwestern Medical Center; Estados UnidosFil: Sakata, Ichiro. University of Texas. Southwestern Medical Center; Estados UnidosFil: Kohno, Dasuke. University of Texas. Southwestern Medical Center; Estados UnidosFil: Perello, Mario. University of Texas. Southwestern Medical Center; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Lawrence, Serri Osborne. University of Texas. Southwestern Medical Center; Estados UnidosFil: Repa, Joyce R.. University of Texas. Southwestern Medical Center; Estados UnidosFil: Zigman, Jeffrey M. University of Texas. Southwestern Medical Center; Estados UnidosOxford University Press2011-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/85915Chuang, Jen Chieh; Sakata, Ichiro; Kohno, Dasuke; Perello, Mario; Lawrence, Serri Osborne; et al.; Ghrelin directly stimulates glucagon secretion from pancreatic α-cells; Oxford University Press; Molecular Endocrinology; 25; 9; 9-2011; 1600-16110888-88091944-9917CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1210/me.2011-1001info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/mend/article/25/9/1600/2614853info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:09:36Zoai:ri.conicet.gov.ar:11336/85915instacron: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 10:09:37.214CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ghrelin directly stimulates glucagon secretion from pancreatic α-cells
title Ghrelin directly stimulates glucagon secretion from pancreatic α-cells
spellingShingle Ghrelin directly stimulates glucagon secretion from pancreatic α-cells
Chuang, Jen Chieh
LEPTINA
GHRELINA
PEPTIDE HORMONE
GLUCAGON
title_short Ghrelin directly stimulates glucagon secretion from pancreatic α-cells
title_full Ghrelin directly stimulates glucagon secretion from pancreatic α-cells
title_fullStr Ghrelin directly stimulates glucagon secretion from pancreatic α-cells
title_full_unstemmed Ghrelin directly stimulates glucagon secretion from pancreatic α-cells
title_sort Ghrelin directly stimulates glucagon secretion from pancreatic α-cells
dc.creator.none.fl_str_mv Chuang, Jen Chieh
Sakata, Ichiro
Kohno, Dasuke
Perello, Mario
Lawrence, Serri Osborne
Repa, Joyce R.
Zigman, Jeffrey M
author Chuang, Jen Chieh
author_facet Chuang, Jen Chieh
Sakata, Ichiro
Kohno, Dasuke
Perello, Mario
Lawrence, Serri Osborne
Repa, Joyce R.
Zigman, Jeffrey M
author_role author
author2 Sakata, Ichiro
Kohno, Dasuke
Perello, Mario
Lawrence, Serri Osborne
Repa, Joyce R.
Zigman, Jeffrey M
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv LEPTINA
GHRELINA
PEPTIDE HORMONE
GLUCAGON
topic LEPTINA
GHRELINA
PEPTIDE HORMONE
GLUCAGON
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Previous work has demonstrated that the peptide hormone ghrelin raises blood glucose. Such has been attributed to ghrelin's ability to enhance GH secretion, restrict insulin release, and/or reduce insulin sensitivity. Ghrelin's reported effects on glucagon have been inconsistent. Here, both animal- and cell-based systems were used to determine the role of glucagon in mediating ghrelin's effects on blood glucose. The tissue and cell distribution of ghrelin receptors (GHSR) was evaluated by quantitative PCR and histochemistry. Plasma glucagon levels were determined following acute acyl-ghrelin injections and in pharmacological and/or transgenic mouse models of ghrelin overexpression and GHSR deletion. Isolated mouse islets and the α-cell lines αTC1 and InR1G9 were used to evaluate ghrelin's effects on glucagon secretion and the role of calcium and ERK in this activity. GHSR mRNA was abundantly expressed in mouse islets and colocalized with glucagon in α-cells. Elevation of acyl-ghrelin acutely (after sc administration, such that physiologically relevant plasma ghrelin levels were achieved) and chronically (by slow-releasing osmotic pumps and as observed in transgenic mice harboring ghrelinomas) led to higher plasma glucagon and increased blood glucose. Conversely, genetic GHSR deletion was associated with lower plasma glucagon and reduced fasting blood glucose. Acyl-ghrelin increased glucagon secretion in a dosedependent manner from mouse islets and α-cell lines, in a manner requiring elevation of intracellular calcium and phosphorylation of ERK. Our study shows that ghrelin's regulation of blood glucose involves direct stimulation of glucagon secretion from α-cells and introduces the ghrelin-glucagon axis as an important mechanism controlling glycemia under fasting conditions.
Fil: Chuang, Jen Chieh. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Sakata, Ichiro. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Kohno, Dasuke. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Perello, Mario. University of Texas. Southwestern Medical Center; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Lawrence, Serri Osborne. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Repa, Joyce R.. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Zigman, Jeffrey M. University of Texas. Southwestern Medical Center; Estados Unidos
description Previous work has demonstrated that the peptide hormone ghrelin raises blood glucose. Such has been attributed to ghrelin's ability to enhance GH secretion, restrict insulin release, and/or reduce insulin sensitivity. Ghrelin's reported effects on glucagon have been inconsistent. Here, both animal- and cell-based systems were used to determine the role of glucagon in mediating ghrelin's effects on blood glucose. The tissue and cell distribution of ghrelin receptors (GHSR) was evaluated by quantitative PCR and histochemistry. Plasma glucagon levels were determined following acute acyl-ghrelin injections and in pharmacological and/or transgenic mouse models of ghrelin overexpression and GHSR deletion. Isolated mouse islets and the α-cell lines αTC1 and InR1G9 were used to evaluate ghrelin's effects on glucagon secretion and the role of calcium and ERK in this activity. GHSR mRNA was abundantly expressed in mouse islets and colocalized with glucagon in α-cells. Elevation of acyl-ghrelin acutely (after sc administration, such that physiologically relevant plasma ghrelin levels were achieved) and chronically (by slow-releasing osmotic pumps and as observed in transgenic mice harboring ghrelinomas) led to higher plasma glucagon and increased blood glucose. Conversely, genetic GHSR deletion was associated with lower plasma glucagon and reduced fasting blood glucose. Acyl-ghrelin increased glucagon secretion in a dosedependent manner from mouse islets and α-cell lines, in a manner requiring elevation of intracellular calcium and phosphorylation of ERK. Our study shows that ghrelin's regulation of blood glucose involves direct stimulation of glucagon secretion from α-cells and introduces the ghrelin-glucagon axis as an important mechanism controlling glycemia under fasting conditions.
publishDate 2011
dc.date.none.fl_str_mv 2011-09
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/11336/85915
Chuang, Jen Chieh; Sakata, Ichiro; Kohno, Dasuke; Perello, Mario; Lawrence, Serri Osborne; et al.; Ghrelin directly stimulates glucagon secretion from pancreatic α-cells; Oxford University Press; Molecular Endocrinology; 25; 9; 9-2011; 1600-1611
0888-8809
1944-9917
CONICET Digital
CONICET
url http://hdl.handle.net/11336/85915
identifier_str_mv Chuang, Jen Chieh; Sakata, Ichiro; Kohno, Dasuke; Perello, Mario; Lawrence, Serri Osborne; et al.; Ghrelin directly stimulates glucagon secretion from pancreatic α-cells; Oxford University Press; Molecular Endocrinology; 25; 9; 9-2011; 1600-1611
0888-8809
1944-9917
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1210/me.2011-1001
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/mend/article/25/9/1600/2614853
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/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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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