Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat

Show simple item record Smith, Greg en Chaussade, Claire en Vickers, Mark en Shepherd, Peter en 2012-03-29T01:15:17Z en 2008 en
dc.identifier.citation Diabetologia 51(12):2309-2317 Dec 2008 en
dc.identifier.issn 0012-186X en
dc.identifier.uri en
dc.description.abstract Aims/hypothesis Use of the second-generation antipsychotic drugs (SGAs) results in the development of obesity and a type 2 diabetes-like syndrome. We hypothesised that, in addition to the insulin resistance associated with the obesity, the SGAs might have acute effects on glucose metabolism that could contribute to the derangements in glucose metabolism. Methods We investigated the effects of therapeutically relevant levels of three different antipsychotic medications (haloperidol, quetiapine and clozapine) on glucose tolerance, measures of insulin resistance and hepatic glucose production, and on insulin and glucagon secretion in rats. Results We found that these drugs induce impaired glucose tolerance in rats that is associated with increased insulin secretion (clozapine>quetiapine>haloperidol) but is independent of weight gain. However, Akt/protein kinase B activation is normal, and at these levels of drug there was no effect on insulin action in fat cells or soleus muscle, and no effect on insulin sensitivity as evaluated by insulin tolerance tests. We show that clozapine induces increased glucose levels following pyruvate and glycerol challenges, indicating an increase in hepatic glucose output (HGO). Increased HGO would in turn increase insulin release and would explain the apparent phenotype mimicking insulin resistance.We provide evidence that this effect could at least in part be mediated by a stimulation of glucagon secretion. Conclusions/interpretation Our findings indicate that SGAs can cause acute derangements in glucose metabolism that are not caused by a direct induction of insulin resistance but act via an increase in glucagon secretion and thus stimulation of hepatic glucose production. en
dc.publisher Springer Verlag en
dc.relation.ispartofseries Diabetologia en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from: en
dc.rights.uri en
dc.title Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat en
dc.type Journal Article en
dc.identifier.doi 10.1007/s00125-008-1152-3 en
pubs.issue 12 en
pubs.begin-page 2309 en
pubs.volume 51 en
dc.rights.holder Copyright: Springer Verlag en
dc.identifier.pmid 18843478 en
pubs.end-page 2317 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 81380 en Liggins Institute en Medical and Health Sciences en Medical Sciences en Molecular Medicine en Science en Science Research en Maurice Wilkins Centre (2010-2014) en
pubs.record-created-at-source-date 2010-09-01 en
pubs.dimensions-id 18843478 en

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