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

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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...

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Autores principales:	García-Tornadú, I., Ornstein, A.M., Chamson-Reig, A., Wheeler, M.B., Hill, D.J., Arany, E., Rubinstein, M., Becu-Villalobos, D.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2010
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00137227_v151_n4_p1441_GarciaTornadu
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paperaa:paper_00137227_v151_n4_p1441_GarciaTornadu2023-06-12T16:41:40Z Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance Endocrinology 2010;151(4):1441-1450 García-Tornadú, I. Ornstein, A.M. Chamson-Reig, A. Wheeler, M.B. Hill, D.J. Arany, E. Rubinstein, M. Becu-Villalobos, D. 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 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. 2010 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00137227_v151_n4_p1441_GarciaTornadu
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
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
spellingShingle	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 García-Tornadú, I. Ornstein, A.M. Chamson-Reig, A. Wheeler, M.B. Hill, D.J. Arany, E. Rubinstein, M. Becu-Villalobos, D. Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
topic_facet	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
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.
format	Artículo Artículo publishedVersion
author	García-Tornadú, I. Ornstein, A.M. Chamson-Reig, A. Wheeler, M.B. Hill, D.J. Arany, E. Rubinstein, M. Becu-Villalobos, D.
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_sort	García-Tornadú, I.
title	Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
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
publishDate	2010
url	http://hdl.handle.net/20.500.12110/paper_00137227_v151_n4_p1441_GarciaTornadu
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_version_	1769810072539496448

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

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