Skip to main content
Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance
  • Isabel García-Tornadú, Consejo Nacional de Investigaciones Científicas y Técnicas
  • Ana M. Ornstein, Consejo Nacional de Investigaciones Científicas y Técnicas
  • Astrid Chamson-Reig, Lawson Health Research Institute
  • Michael B. Wheeler, University of Toronto
  • David J. Hill, Lawson Health Research Institute
  • Edith Arany, Lawson Health Research Institute
  • Marcelo Rubinstein, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Buenos Aires
  • Damasia Becu-Villalobos, Consejo Nacional de Investigaciones Científicas y Técnicas
Document Type
Publication Date
URL with Digital Object Identifier

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.

Citation Information
Isabel García-Tornadú, Ana M. Ornstein, Astrid Chamson-Reig, Michael B. Wheeler, et al.. "Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance" Endocrinology Vol. 151 Iss. 4 (2010) p. 1441 - 1450
Available at: