INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
artículos
Título:
Disruption of the Dopamine D2 Receptor Impairs Insulin Secretion and Causes Glucose Intolerance
Autor/es:
GARCÍA-TORNADÚ I; ORSTEIN, A.M.; CHAMSON-REIG, A.; WHEELER, M.B. ; HILL, D.J.; ARANY E; RUBINSTEIN M; BECU-VILLALOBOS D
Revista:
ENDOCRINOLOGY
Editorial:
ENDOCRINE SOC
Referencias:
Año: 2010 p. 1441 - 1450
ISSN:
0013-7227
Resumen:
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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 -cell mass in
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.