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
- Institución
- Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
- OAI Identificador
- paperaa:paper_00137227_v151_n4_p1441_GarciaTornadu
Ver los metadatos del registro completo
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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 http://creativecommons.org/licenses/by/2.5/ar |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by/2.5/ar |
dc.format.none.fl_str_mv |
application/pdf |
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) |
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Biblioteca Digital (UBA-FCEN) |
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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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