Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance

Autores
García-Tornadú, I.; Ornstein, A.M.; Chamson-Reig, A.; Wheeler, M.B.; Hill, D.J.; Arany, E.; Rubinstein, M.; Becu-Villalobos, D.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The relationship between antidopaminergic drugs and glucose has not been extensively studied, even though chronic neuroleptic treatment causes hyperinsulinemia in normal subjects or is associated with diabetes in psychiatric patients. We sought to evaluate dopamine D2 receptor (D2R) participation in pancreatic function. Glucose homeostasis was studied in D2R knockout mice (Drd2-/-) mice and in isolated islets from wild-type and Drd2-/- mice, using different pharmacological tools. Pancreas immunohistochemistry was performed. Drd2-/- male mice exhibited an impairment of insulin response to glucose and high fasting glucose levels and were glucose intolerant. Glucose intolerance resulted from a blunted insulin secretory response, rather than insulin resistance, as shown by glucose-stimulated insulin secretion tests (GSIS) in vivo and in vitro and by a conserved insulin tolerance test in vivo. On the other hand, short-term treatment with cabergoline, a dopamine agonist, resulted in glucose intolerance and decreased insulin response to glucose in wild-type but not in Drd2 -/- mice; this effect was partially prevented by haloperidol, a D2R antagonist. In vitro results indicated that GSIS was impaired in islets from Drd2-/- mice and that only in wild-type islets did dopamine inhibit GSIS, an effect that was blocked by a D2R but not a D1R antagonist. Finally, immunohistochemistry showed a diminished pancreatic β-cell mass in Drd2-/-mice and decreasedβ-cell replication in 2-month-old Drd2-/- mice. Pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops. Copyright © 2010 by The Endocrine Society.
Fil:García-Tornadú, I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Chamson-Reig, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fuente
Endocrinology 2010;151(4):1441-1450
Materia
cabergoline
dopamine 2 receptor
haloperidol
animal cell
animal experiment
animal model
animal tissue
article
cell division
cell isolation
drug mechanism
glucose homeostasis
glucose intolerance
immunohistochemistry
in vitro study
in vivo study
insulin release
insulin tolerance test
male
mouse
nonhuman
pancreas function
pancreas islet beta cell
pancreas islet cell
priority journal
Analysis of Variance
Animals
Blood Glucose
Cell Proliferation
Dopamine Agonists
Dopamine Antagonists
Ergolines
Female
Glucose
Glucose Intolerance
Haloperidol
Immunohistochemistry
Insulin
Insulin-Like Growth Factor I
Male
Mice
Mice, Knockout
Pancreas
Prolactin
Radioimmunoassay
Receptors, Dopamine D2
Time Factors
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/2.5/ar
Repositorio
Biblioteca Digital (UBA-FCEN)
Institución
Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
OAI Identificador
paperaa:paper_00137227_v151_n4_p1441_GarciaTornadu

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oai_identifier_str paperaa:paper_00137227_v151_n4_p1441_GarciaTornadu
network_acronym_str BDUBAFCEN
repository_id_str 1896
network_name_str Biblioteca Digital (UBA-FCEN)
spelling Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intoleranceGarcía-Tornadú, I.Ornstein, A.M.Chamson-Reig, A.Wheeler, M.B.Hill, D.J.Arany, E.Rubinstein, M.Becu-Villalobos, D.cabergolinedopamine 2 receptorhaloperidolanimal cellanimal experimentanimal modelanimal tissuearticlecell divisioncell isolationdrug mechanismglucose homeostasisglucose intoleranceimmunohistochemistryin vitro studyin vivo studyinsulin releaseinsulin tolerance testmalemousenonhumanpancreas functionpancreas islet beta cellpancreas islet cellpriority journalAnalysis of VarianceAnimalsBlood GlucoseCell ProliferationDopamine AgonistsDopamine AntagonistsErgolinesFemaleGlucoseGlucose IntoleranceHaloperidolImmunohistochemistryInsulinInsulin-Like Growth Factor IMaleMiceMice, KnockoutPancreasProlactinRadioimmunoassayReceptors, Dopamine D2Time FactorsThe relationship between antidopaminergic drugs and glucose has not been extensively studied, even though chronic neuroleptic treatment causes hyperinsulinemia in normal subjects or is associated with diabetes in psychiatric patients. We sought to evaluate dopamine D2 receptor (D2R) participation in pancreatic function. Glucose homeostasis was studied in D2R knockout mice (Drd2-/-) mice and in isolated islets from wild-type and Drd2-/- mice, using different pharmacological tools. Pancreas immunohistochemistry was performed. Drd2-/- male mice exhibited an impairment of insulin response to glucose and high fasting glucose levels and were glucose intolerant. Glucose intolerance resulted from a blunted insulin secretory response, rather than insulin resistance, as shown by glucose-stimulated insulin secretion tests (GSIS) in vivo and in vitro and by a conserved insulin tolerance test in vivo. On the other hand, short-term treatment with cabergoline, a dopamine agonist, resulted in glucose intolerance and decreased insulin response to glucose in wild-type but not in Drd2 -/- mice; this effect was partially prevented by haloperidol, a D2R antagonist. In vitro results indicated that GSIS was impaired in islets from Drd2-/- mice and that only in wild-type islets did dopamine inhibit GSIS, an effect that was blocked by a D2R but not a D1R antagonist. Finally, immunohistochemistry showed a diminished pancreatic β-cell mass in Drd2-/-mice and decreasedβ-cell replication in 2-month-old Drd2-/- mice. Pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops. Copyright © 2010 by The Endocrine Society.Fil:García-Tornadú, I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Chamson-Reig, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.2010info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12110/paper_00137227_v151_n4_p1441_GarciaTornaduEndocrinology 2010;151(4):1441-1450reponame:Biblioteca Digital (UBA-FCEN)instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesinstacron:UBA-FCENenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/2.5/ar2025-09-29T13:42:52Zpaperaa:paper_00137227_v151_n4_p1441_GarciaTornaduInstitucionalhttps://digital.bl.fcen.uba.ar/Universidad públicaNo correspondehttps://digital.bl.fcen.uba.ar/cgi-bin/oaiserver.cgiana@bl.fcen.uba.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:18962025-09-29 13:42:53.681Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesfalse
dc.title.none.fl_str_mv Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
title Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
spellingShingle Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
García-Tornadú, I.
cabergoline
dopamine 2 receptor
haloperidol
animal cell
animal experiment
animal model
animal tissue
article
cell division
cell isolation
drug mechanism
glucose homeostasis
glucose intolerance
immunohistochemistry
in vitro study
in vivo study
insulin release
insulin tolerance test
male
mouse
nonhuman
pancreas function
pancreas islet beta cell
pancreas islet cell
priority journal
Analysis of Variance
Animals
Blood Glucose
Cell Proliferation
Dopamine Agonists
Dopamine Antagonists
Ergolines
Female
Glucose
Glucose Intolerance
Haloperidol
Immunohistochemistry
Insulin
Insulin-Like Growth Factor I
Male
Mice
Mice, Knockout
Pancreas
Prolactin
Radioimmunoassay
Receptors, Dopamine D2
Time Factors
title_short Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
title_full Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
title_fullStr Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
title_full_unstemmed Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
title_sort Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
dc.creator.none.fl_str_mv García-Tornadú, I.
Ornstein, A.M.
Chamson-Reig, A.
Wheeler, M.B.
Hill, D.J.
Arany, E.
Rubinstein, M.
Becu-Villalobos, D.
author García-Tornadú, I.
author_facet García-Tornadú, I.
Ornstein, A.M.
Chamson-Reig, A.
Wheeler, M.B.
Hill, D.J.
Arany, E.
Rubinstein, M.
Becu-Villalobos, D.
author_role author
author2 Ornstein, A.M.
Chamson-Reig, A.
Wheeler, M.B.
Hill, D.J.
Arany, E.
Rubinstein, M.
Becu-Villalobos, D.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv cabergoline
dopamine 2 receptor
haloperidol
animal cell
animal experiment
animal model
animal tissue
article
cell division
cell isolation
drug mechanism
glucose homeostasis
glucose intolerance
immunohistochemistry
in vitro study
in vivo study
insulin release
insulin tolerance test
male
mouse
nonhuman
pancreas function
pancreas islet beta cell
pancreas islet cell
priority journal
Analysis of Variance
Animals
Blood Glucose
Cell Proliferation
Dopamine Agonists
Dopamine Antagonists
Ergolines
Female
Glucose
Glucose Intolerance
Haloperidol
Immunohistochemistry
Insulin
Insulin-Like Growth Factor I
Male
Mice
Mice, Knockout
Pancreas
Prolactin
Radioimmunoassay
Receptors, Dopamine D2
Time Factors
topic cabergoline
dopamine 2 receptor
haloperidol
animal cell
animal experiment
animal model
animal tissue
article
cell division
cell isolation
drug mechanism
glucose homeostasis
glucose intolerance
immunohistochemistry
in vitro study
in vivo study
insulin release
insulin tolerance test
male
mouse
nonhuman
pancreas function
pancreas islet beta cell
pancreas islet cell
priority journal
Analysis of Variance
Animals
Blood Glucose
Cell Proliferation
Dopamine Agonists
Dopamine Antagonists
Ergolines
Female
Glucose
Glucose Intolerance
Haloperidol
Immunohistochemistry
Insulin
Insulin-Like Growth Factor I
Male
Mice
Mice, Knockout
Pancreas
Prolactin
Radioimmunoassay
Receptors, Dopamine D2
Time Factors
dc.description.none.fl_txt_mv The relationship between antidopaminergic drugs and glucose has not been extensively studied, even though chronic neuroleptic treatment causes hyperinsulinemia in normal subjects or is associated with diabetes in psychiatric patients. We sought to evaluate dopamine D2 receptor (D2R) participation in pancreatic function. Glucose homeostasis was studied in D2R knockout mice (Drd2-/-) mice and in isolated islets from wild-type and Drd2-/- mice, using different pharmacological tools. Pancreas immunohistochemistry was performed. Drd2-/- male mice exhibited an impairment of insulin response to glucose and high fasting glucose levels and were glucose intolerant. Glucose intolerance resulted from a blunted insulin secretory response, rather than insulin resistance, as shown by glucose-stimulated insulin secretion tests (GSIS) in vivo and in vitro and by a conserved insulin tolerance test in vivo. On the other hand, short-term treatment with cabergoline, a dopamine agonist, resulted in glucose intolerance and decreased insulin response to glucose in wild-type but not in Drd2 -/- mice; this effect was partially prevented by haloperidol, a D2R antagonist. In vitro results indicated that GSIS was impaired in islets from Drd2-/- mice and that only in wild-type islets did dopamine inhibit GSIS, an effect that was blocked by a D2R but not a D1R antagonist. Finally, immunohistochemistry showed a diminished pancreatic β-cell mass in Drd2-/-mice and decreasedβ-cell replication in 2-month-old Drd2-/- mice. Pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops. Copyright © 2010 by The Endocrine Society.
Fil:García-Tornadú, I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Chamson-Reig, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
description The relationship between antidopaminergic drugs and glucose has not been extensively studied, even though chronic neuroleptic treatment causes hyperinsulinemia in normal subjects or is associated with diabetes in psychiatric patients. We sought to evaluate dopamine D2 receptor (D2R) participation in pancreatic function. Glucose homeostasis was studied in D2R knockout mice (Drd2-/-) mice and in isolated islets from wild-type and Drd2-/- mice, using different pharmacological tools. Pancreas immunohistochemistry was performed. Drd2-/- male mice exhibited an impairment of insulin response to glucose and high fasting glucose levels and were glucose intolerant. Glucose intolerance resulted from a blunted insulin secretory response, rather than insulin resistance, as shown by glucose-stimulated insulin secretion tests (GSIS) in vivo and in vitro and by a conserved insulin tolerance test in vivo. On the other hand, short-term treatment with cabergoline, a dopamine agonist, resulted in glucose intolerance and decreased insulin response to glucose in wild-type but not in Drd2 -/- mice; this effect was partially prevented by haloperidol, a D2R antagonist. In vitro results indicated that GSIS was impaired in islets from Drd2-/- mice and that only in wild-type islets did dopamine inhibit GSIS, an effect that was blocked by a D2R but not a D1R antagonist. Finally, immunohistochemistry showed a diminished pancreatic β-cell mass in Drd2-/-mice and decreasedβ-cell replication in 2-month-old Drd2-/- mice. Pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops. Copyright © 2010 by The Endocrine Society.
publishDate 2010
dc.date.none.fl_str_mv 2010
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/20.500.12110/paper_00137227_v151_n4_p1441_GarciaTornadu
url http://hdl.handle.net/20.500.12110/paper_00137227_v151_n4_p1441_GarciaTornadu
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/2.5/ar
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dc.source.none.fl_str_mv Endocrinology 2010;151(4):1441-1450
reponame:Biblioteca Digital (UBA-FCEN)
instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron:UBA-FCEN
reponame_str Biblioteca Digital (UBA-FCEN)
collection Biblioteca Digital (UBA-FCEN)
instname_str Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron_str UBA-FCEN
institution UBA-FCEN
repository.name.fl_str_mv Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
repository.mail.fl_str_mv ana@bl.fcen.uba.ar
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