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Abstract:

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.

Registro:

Documento: Artículo
Título:Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
Autor:García-Tornadú, I.; Ornstein, A.M.; Chamson-Reig, A.; Wheeler, M.B.; Hill, D.J.; Arany, E.; Rubinstein, M.; Becu-Villalobos, D.
Filiación:Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina
Lawson Health Research Institute, London, ON N6A 4V2, Canada
Departments of Physiology and Medicine, Endocrinology and Diabetes Research Group, University of Toronto, ON M5S 1A8, Canada
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, CONICET, Buenos Aires 2490, Argentina
Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, University of Buenos Aires, Buenos Aires 1428, Argentina
Palabras clave: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
Año:2010
Volumen:151
Número:4
Página de inicio:1441
Página de fin:1450
DOI: http://dx.doi.org/10.1210/en.2009-0996
Título revista:Endocrinology
Título revista abreviado:Endocrinology
ISSN:00137227
CODEN:ENDOA
CAS:cabergoline, 81409-90-7; haloperidol, 52-86-8; Blood Glucose; Dopamine Agonists; Dopamine Antagonists; Ergolines; Glucose, 50-99-7; Haloperidol, 52-86-8; Insulin, 11061-68-0; Insulin-Like Growth Factor I, 67763-96-6; Prolactin, 9002-62-4; Receptors, Dopamine D2; cabergoline, 81409-90-7
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00137227_v151_n4_p1441_GarciaTornadu.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v151_n4_p1441_GarciaTornadu

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Citas:

---------- APA ----------
García-Tornadú, I., Ornstein, A.M., Chamson-Reig, A., Wheeler, M.B., Hill, D.J., Arany, E., Rubinstein, M.,..., Becu-Villalobos, D. (2010) . Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance. Endocrinology, 151(4), 1441-1450.
http://dx.doi.org/10.1210/en.2009-0996
---------- CHICAGO ----------
García-Tornadú, I., Ornstein, A.M., Chamson-Reig, A., Wheeler, M.B., Hill, D.J., Arany, E., et al. "Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance" . Endocrinology 151, no. 4 (2010) : 1441-1450.
http://dx.doi.org/10.1210/en.2009-0996
---------- MLA ----------
García-Tornadú, I., Ornstein, A.M., Chamson-Reig, A., Wheeler, M.B., Hill, D.J., Arany, E., et al. "Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance" . Endocrinology, vol. 151, no. 4, 2010, pp. 1441-1450.
http://dx.doi.org/10.1210/en.2009-0996
---------- VANCOUVER ----------
García-Tornadú, I., Ornstein, A.M., Chamson-Reig, A., Wheeler, M.B., Hill, D.J., Arany, E., et al. Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance. Endocrinology. 2010;151(4):1441-1450.
http://dx.doi.org/10.1210/en.2009-0996