Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion

Aims: To investigate the effects of the second generation antipsychotic (R/S)-amisulpride, and the chirally purified enantiomers, on glucose homeostasis in diet-induced obese (DIO) mice. Methods: Normal and DIO mice were treated with pharmacologically relevant doses of amisulpride prior to oral gluc...

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Main Authors: Roix, J., Decrescenzo, G., Cheung, P., Ciallella, J., Sulpice, T., Saha, S., Halse, Rhiannon
Format: Journal Article
Published: 2012
Online Access:http://hdl.handle.net/20.500.11937/55579
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author Roix, J.
Decrescenzo, G.
Cheung, P.
Ciallella, J.
Sulpice, T.
Saha, S.
Halse, Rhiannon
author_facet Roix, J.
Decrescenzo, G.
Cheung, P.
Ciallella, J.
Sulpice, T.
Saha, S.
Halse, Rhiannon
author_sort Roix, J.
building Curtin Institutional Repository
collection Online Access
description Aims: To investigate the effects of the second generation antipsychotic (R/S)-amisulpride, and the chirally purified enantiomers, on glucose homeostasis in diet-induced obese (DIO) mice. Methods: Normal and DIO mice were treated with pharmacologically relevant doses of amisulpride prior to oral glucose tolerance tests (OGTTs). Blood glucose, insulin, glucagon-like peptide-1, prolactin and amisulpride drug levels were determined. Results: Racemic amisulpride significantly reduced glucose excursions during OGTT in both normal and DIO mice. This potent effect was preserved with the 'off-isomer', R-amisulpride (ED 50 1 mg/kg). Insulin secretion was significantly increased with R-amisulpride with only a minor increase in prolactin levels. Conclusions: Amisulpride has antidiabetic actions in DIO mice resulting from increased insulin secretion. This provides some explanation for why amisulpride, unlike other atypical antipsychotics, is not diabetogenic in man. Furthermore, the observation that R-amisulpride is also antidiabetic and has minimal impact on prolactin levels presents the opportunity for development of this isomer as an antidiabetic agent. © 2011 Blackwell Publishing Ltd.
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spelling curtin-20.500.11937-555792017-09-13T16:11:01Z Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion Roix, J. Decrescenzo, G. Cheung, P. Ciallella, J. Sulpice, T. Saha, S. Halse, Rhiannon Aims: To investigate the effects of the second generation antipsychotic (R/S)-amisulpride, and the chirally purified enantiomers, on glucose homeostasis in diet-induced obese (DIO) mice. Methods: Normal and DIO mice were treated with pharmacologically relevant doses of amisulpride prior to oral glucose tolerance tests (OGTTs). Blood glucose, insulin, glucagon-like peptide-1, prolactin and amisulpride drug levels were determined. Results: Racemic amisulpride significantly reduced glucose excursions during OGTT in both normal and DIO mice. This potent effect was preserved with the 'off-isomer', R-amisulpride (ED 50 1 mg/kg). Insulin secretion was significantly increased with R-amisulpride with only a minor increase in prolactin levels. Conclusions: Amisulpride has antidiabetic actions in DIO mice resulting from increased insulin secretion. This provides some explanation for why amisulpride, unlike other atypical antipsychotics, is not diabetogenic in man. Furthermore, the observation that R-amisulpride is also antidiabetic and has minimal impact on prolactin levels presents the opportunity for development of this isomer as an antidiabetic agent. © 2011 Blackwell Publishing Ltd. 2012 Journal Article http://hdl.handle.net/20.500.11937/55579 10.1111/j.1463-1326.2011.01529.x restricted
spellingShingle Roix, J.
Decrescenzo, G.
Cheung, P.
Ciallella, J.
Sulpice, T.
Saha, S.
Halse, Rhiannon
Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion
title Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion
title_full Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion
title_fullStr Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion
title_full_unstemmed Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion
title_short Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion
title_sort effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion
url http://hdl.handle.net/20.500.11937/55579