Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice

Autores
Bonaventura, Maria Marta; Crivello, Martin; Ferreira, Maria Laura; Repetto, Martín; Cymeryng, Cora Betriz; Libertun, Carlos; Lux, Victoria Adela R.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
γ-Aminobutyric acid (GABA) inhibits insulin secretion through GABAB receptors in pancreatic β-cells. We investigated whether GABAB receptors participated in the regulation of glucose homeostasis in vivo. BALB/c mice acutely pre-injected with the GABAB receptor agonist baclofen (7.5 mg/kg, i.p.) presented glucose intolerance and diminished insulin secretion during a glucose tolerance test (GTT, 2 g/kg body weight, i.p.). The GABAB receptor antagonist 2-hydroxysaclofen (15 mg/kg, i.p.) improved the GTT and reversed the baclofen effect. Also a slight increase in insulin secretion was observed with 2-hydroxysaclofen. In incubated islets 1.10−5 M baclofen inhibited 20 mM glucose-induced insulin secretion and this effect was reversed by coincubation with 1.10−5 M 2-hydroxysaclofen. In chronically-treated animals (18 days) both the receptor agonist (5 mg/kg/day i.p.) and the receptor antagonist (10 mg/kg/day i.p.) induced impaired GTTs; the receptor antagonist, but not the agonist, also induced a decrease in insulin secretion. No alterations in insulin tolerance tests, body weight and food intake were observed with the treatments. In addition glucagon, insulin-like growth factor I, prolactin, corticosterone and growth hormone, other hormones involved in glucose metabolism regulation, were not affected by chronic baclofen or 2-hydroxysaclofen. In islets obtained from chronically injected animals with baclofen, 2-hydroxysaclofen or saline (as above), GABAB2 mRNA expression was not altered. Results demonstrate that GABAB receptors are involved in the regulation of glucose homeostasis in vivo. Treatment with receptor agonists or antagonists, given acutely or chronically, altered glucose homeostasis and insulin secretion alerting to the need to evaluate glucose metabolism during the clinical use of these drugs.
Fil: Bonaventura, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Crivello, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Ferreira, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Repetto, Martín. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Libertun, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
FOOD INTAKE
GABA B RECEPTOR AGONIST AND ANTAGONIST
GLYCEMIA
INSULIN
SERUM HORMONE
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:11336/194287
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effects of GABAB receptor agonists and antagonists on glycemia regulation in miceBonaventura, Maria MartaCrivello, MartinFerreira, Maria LauraRepetto, MartínCymeryng, Cora BetrizLibertun, CarlosLux, Victoria Adela R.FOOD INTAKEGABA B RECEPTOR AGONIST AND ANTAGONISTGLYCEMIAINSULINSERUM HORMONEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3γ-Aminobutyric acid (GABA) inhibits insulin secretion through GABAB receptors in pancreatic β-cells. We investigated whether GABAB receptors participated in the regulation of glucose homeostasis in vivo. BALB/c mice acutely pre-injected with the GABAB receptor agonist baclofen (7.5 mg/kg, i.p.) presented glucose intolerance and diminished insulin secretion during a glucose tolerance test (GTT, 2 g/kg body weight, i.p.). The GABAB receptor antagonist 2-hydroxysaclofen (15 mg/kg, i.p.) improved the GTT and reversed the baclofen effect. Also a slight increase in insulin secretion was observed with 2-hydroxysaclofen. In incubated islets 1.10−5 M baclofen inhibited 20 mM glucose-induced insulin secretion and this effect was reversed by coincubation with 1.10−5 M 2-hydroxysaclofen. In chronically-treated animals (18 days) both the receptor agonist (5 mg/kg/day i.p.) and the receptor antagonist (10 mg/kg/day i.p.) induced impaired GTTs; the receptor antagonist, but not the agonist, also induced a decrease in insulin secretion. No alterations in insulin tolerance tests, body weight and food intake were observed with the treatments. In addition glucagon, insulin-like growth factor I, prolactin, corticosterone and growth hormone, other hormones involved in glucose metabolism regulation, were not affected by chronic baclofen or 2-hydroxysaclofen. In islets obtained from chronically injected animals with baclofen, 2-hydroxysaclofen or saline (as above), GABAB2 mRNA expression was not altered. Results demonstrate that GABAB receptors are involved in the regulation of glucose homeostasis in vivo. Treatment with receptor agonists or antagonists, given acutely or chronically, altered glucose homeostasis and insulin secretion alerting to the need to evaluate glucose metabolism during the clinical use of these drugs.Fil: Bonaventura, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Crivello, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ferreira, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Repetto, Martín. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Libertun, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaElsevier Science2012-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/194287Bonaventura, Maria Marta; Crivello, Martin; Ferreira, Maria Laura; Repetto, Martín; Cymeryng, Cora Betriz; et al.; Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice; Elsevier Science; European Journal of Pharmacology; 677; 1-3; 2-2012; 188-1960014-2999CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0014299911015329info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2011.12.013info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:05:04Zoai:ri.conicet.gov.ar:11336/194287instacron: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 10:05:04.971CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice
title Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice
spellingShingle Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice
Bonaventura, Maria Marta
FOOD INTAKE
GABA B RECEPTOR AGONIST AND ANTAGONIST
GLYCEMIA
INSULIN
SERUM HORMONE
title_short Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice
title_full Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice
title_fullStr Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice
title_full_unstemmed Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice
title_sort Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice
dc.creator.none.fl_str_mv Bonaventura, Maria Marta
Crivello, Martin
Ferreira, Maria Laura
Repetto, Martín
Cymeryng, Cora Betriz
Libertun, Carlos
Lux, Victoria Adela R.
author Bonaventura, Maria Marta
author_facet Bonaventura, Maria Marta
Crivello, Martin
Ferreira, Maria Laura
Repetto, Martín
Cymeryng, Cora Betriz
Libertun, Carlos
Lux, Victoria Adela R.
author_role author
author2 Crivello, Martin
Ferreira, Maria Laura
Repetto, Martín
Cymeryng, Cora Betriz
Libertun, Carlos
Lux, Victoria Adela R.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv FOOD INTAKE
GABA B RECEPTOR AGONIST AND ANTAGONIST
GLYCEMIA
INSULIN
SERUM HORMONE
topic FOOD INTAKE
GABA B RECEPTOR AGONIST AND ANTAGONIST
GLYCEMIA
INSULIN
SERUM HORMONE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv γ-Aminobutyric acid (GABA) inhibits insulin secretion through GABAB receptors in pancreatic β-cells. We investigated whether GABAB receptors participated in the regulation of glucose homeostasis in vivo. BALB/c mice acutely pre-injected with the GABAB receptor agonist baclofen (7.5 mg/kg, i.p.) presented glucose intolerance and diminished insulin secretion during a glucose tolerance test (GTT, 2 g/kg body weight, i.p.). The GABAB receptor antagonist 2-hydroxysaclofen (15 mg/kg, i.p.) improved the GTT and reversed the baclofen effect. Also a slight increase in insulin secretion was observed with 2-hydroxysaclofen. In incubated islets 1.10−5 M baclofen inhibited 20 mM glucose-induced insulin secretion and this effect was reversed by coincubation with 1.10−5 M 2-hydroxysaclofen. In chronically-treated animals (18 days) both the receptor agonist (5 mg/kg/day i.p.) and the receptor antagonist (10 mg/kg/day i.p.) induced impaired GTTs; the receptor antagonist, but not the agonist, also induced a decrease in insulin secretion. No alterations in insulin tolerance tests, body weight and food intake were observed with the treatments. In addition glucagon, insulin-like growth factor I, prolactin, corticosterone and growth hormone, other hormones involved in glucose metabolism regulation, were not affected by chronic baclofen or 2-hydroxysaclofen. In islets obtained from chronically injected animals with baclofen, 2-hydroxysaclofen or saline (as above), GABAB2 mRNA expression was not altered. Results demonstrate that GABAB receptors are involved in the regulation of glucose homeostasis in vivo. Treatment with receptor agonists or antagonists, given acutely or chronically, altered glucose homeostasis and insulin secretion alerting to the need to evaluate glucose metabolism during the clinical use of these drugs.
Fil: Bonaventura, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Crivello, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Ferreira, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Repetto, Martín. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Libertun, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description γ-Aminobutyric acid (GABA) inhibits insulin secretion through GABAB receptors in pancreatic β-cells. We investigated whether GABAB receptors participated in the regulation of glucose homeostasis in vivo. BALB/c mice acutely pre-injected with the GABAB receptor agonist baclofen (7.5 mg/kg, i.p.) presented glucose intolerance and diminished insulin secretion during a glucose tolerance test (GTT, 2 g/kg body weight, i.p.). The GABAB receptor antagonist 2-hydroxysaclofen (15 mg/kg, i.p.) improved the GTT and reversed the baclofen effect. Also a slight increase in insulin secretion was observed with 2-hydroxysaclofen. In incubated islets 1.10−5 M baclofen inhibited 20 mM glucose-induced insulin secretion and this effect was reversed by coincubation with 1.10−5 M 2-hydroxysaclofen. In chronically-treated animals (18 days) both the receptor agonist (5 mg/kg/day i.p.) and the receptor antagonist (10 mg/kg/day i.p.) induced impaired GTTs; the receptor antagonist, but not the agonist, also induced a decrease in insulin secretion. No alterations in insulin tolerance tests, body weight and food intake were observed with the treatments. In addition glucagon, insulin-like growth factor I, prolactin, corticosterone and growth hormone, other hormones involved in glucose metabolism regulation, were not affected by chronic baclofen or 2-hydroxysaclofen. In islets obtained from chronically injected animals with baclofen, 2-hydroxysaclofen or saline (as above), GABAB2 mRNA expression was not altered. Results demonstrate that GABAB receptors are involved in the regulation of glucose homeostasis in vivo. Treatment with receptor agonists or antagonists, given acutely or chronically, altered glucose homeostasis and insulin secretion alerting to the need to evaluate glucose metabolism during the clinical use of these drugs.
publishDate 2012
dc.date.none.fl_str_mv 2012-02
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/11336/194287
Bonaventura, Maria Marta; Crivello, Martin; Ferreira, Maria Laura; Repetto, Martín; Cymeryng, Cora Betriz; et al.; Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice; Elsevier Science; European Journal of Pharmacology; 677; 1-3; 2-2012; 188-196
0014-2999
CONICET Digital
CONICET
url http://hdl.handle.net/11336/194287
identifier_str_mv Bonaventura, Maria Marta; Crivello, Martin; Ferreira, Maria Laura; Repetto, Martín; Cymeryng, Cora Betriz; et al.; Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice; Elsevier Science; European Journal of Pharmacology; 677; 1-3; 2-2012; 188-196
0014-2999
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://www.sciencedirect.com/science/article/abs/pii/S0014299911015329
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2011.12.013
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
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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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