Abstract:
:Second generation antipsychotics cause derangements in glucose metabolism that are often interpreted as insulin resistance. In previous studies we have shown that this is not classical insulin resistance but the drugs were actually inducing a hyperglycaemic state associated with elevated hepatic glucose output (HGO) and increased levels of glucagon and insulin. However, it remains unclear whether these effects are directly elicited by drug actions in the liver and pancreas, or whether they are indirectly mediated. Here we investigated if clozapine is capable of inducing insulin resistance in the liver or enhancing insulin and glucagon secretion from the pancreas. It was observed that insulin signalling was elevated in livers from animals treated with clozapine indicating there was no insulin resistance in the early steps of insulin signalling. To explore whether the defects arise at later stages of insulin action we used an isolated perfused liver system. In this model, clozapine had no direct effect on insulin's counter regulatory effect on epinephrine-induced HGO. In isolated mouse islets clozapine significantly increased glucose-stimulated insulin secretion while simultaneously blocking glucose-induced reductions in glucagon secretion. We also show that the non-peptidic glucagon receptor like peptide-1 (GLP-1) receptor agonist Boc5 was able to overcome the inhibitory effects of clozapine on glucose metabolism. Taken together these results suggest that clozapine does not have any direct effect on glucose metabolism in the liver but it simultaneously stimulates insulin and glucagon secretion, a situation that would allow for the concurrent presence of high glucose and high insulin levels in treated animals.
journal_name
Schizophr Resjournal_title
Schizophrenia researchauthors
Smith GC,Zhang ZY,Mulvey T,Petersen N,Lach S,Xiu P,Phillips A,Han W,Wang MW,Shepherd PRdoi
10.1016/j.schres.2014.05.003subject
Has Abstractpub_date
2014-08-01 00:00:00pages
128-33issue
1-3eissn
0920-9964issn
1573-2509pii
S0920-9964(14)00230-8journal_volume
157pub_type
杂志文章abstract::Motivational deficits in patients with schizophrenia adversely affect various domains of daily living. This symptom in everyday life situations manifests in a complex behavioral pattern whose root cannot be simplified to an impaired reward-motivation scheme. This study aimed to identify impairment of the salience netw...
journal_title:Schizophrenia research
pub_type: 杂志文章
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更新日期:2018-07-01 00:00:00
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doi:10.1016/s0920-9964(00)00192-4
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pub_type: 杂志文章
doi:10.1016/s0920-9964(02)00295-5
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pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2011-08-01 00:00:00
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pub_type: 杂志文章,多中心研究
doi:10.1016/j.schres.2012.06.032
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更新日期:2017-11-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2011.11.007
更新日期:2012-03-01 00:00:00
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pub_type: 杂志文章,随机对照试验
doi:10.1016/j.schres.2014.12.024
更新日期:2015-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0920-9964(90)90020-8
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2007.11.018
更新日期:2008-02-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2009.08.014
更新日期:2009-11-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(03)00188-9
更新日期:2004-08-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2012.03.024
更新日期:2012-07-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2016.04.050
更新日期:2016-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.schres.2020.09.009
更新日期:2020-09-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2009.03.017
更新日期:2009-06-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.schres.2011.03.029
更新日期:2011-06-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2007.08.027
更新日期:2008-02-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/0920-9964(92)90039-8
更新日期:1992-07-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(02)00527-3
更新日期:2003-04-01 00:00:00
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pub_type: 杂志文章,多中心研究
doi:10.1016/s0920-9964(03)00018-5
更新日期:2003-11-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2015.04.003
更新日期:2015-06-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2012.06.017
更新日期:2012-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.schres.2013.11.023
更新日期:2014-01-01 00:00:00
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pub_type: 杂志文章,随机对照试验
doi:10.1016/j.schres.2015.06.015
更新日期:2015-10-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1016/j.schres.2017.06.049
更新日期:2018-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.schres.2015.08.022
更新日期:2015-10-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.schres.2018.09.006
更新日期:2019-02-01 00:00:00
abstract::Little is known about the impact of family history of psychosis on youth from community samples. To fill this gap, we compared youth with a first-degree relative with psychosis spectrum symptoms (i.e. family history of psychosis spectrum symptoms, FHPS) to youth without FHPS in a cross-sectional analysis of the Philad...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2019.12.021
更新日期:2020-02-01 00:00:00