Clozapine directly increases insulin and glucagon secretion from islets: Implications for impairment of glucose tolerance
文献类型：期刊论文
| 作者 | Smith, G. C.6,7; Zhang, Z. Y.4,5; Mulvey, T.6; Petersend, N.2,8; Lach, S.6; Xiu, P.3; Phillips, A.9; Han, W.2; Wang, M. -W.4,5,6; Shepherd, P. R.1 |
| 刊名 | SCHIZOPHRENIA RESEARCH
 |
| 出版日期 | 2014-08 |
| 卷号 | 157期号:1-3页码:128-133 |
| 关键词 | Clozapine Diabetes Insulin signalling Schizophrenia |
| ISSN号 | 0920-9964 |
| DOI | 10.1016/j.schres.2014.05.003 |
| 文献子类 | Article |
| 英文摘要 | 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. (C) 2014 Elsevier B.V. All rights reserved. |
| WOS关键词 | PEPTIDE-1 RECEPTOR AGONIST ; RAT-LIVER ; IN-VITRO ; OLANZAPINE ; SCHIZOPHRENIA ; ANTIPSYCHOTICS ; METABOLISM ; INTOLERANCE ; RESISTANCE ; BOC5 |
| 资助项目 | Chinese Ministry of Health[2012ZX09304-011] ; Chinese Ministry of Health[2013ZX09507-001] ; Chinese Ministry of Health[2013ZX09507-002] ; New Zealand Health Research Council[10-585] ; New Zealand Foundation for Research, Science and Technology Fellowship[21422-PDFS] |
| WOS研究方向 | Psychiatry |
| 语种 | 英语 |
| WOS记录号 | WOS:000341314100020 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276955]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Wang, M. -W. |
| 作者单位 | 1.Maurice Wilkins Ctr, Auckland, New Zealand; 2.ASTAR, Singapore Bioimaging Consortium, Singapore, Singapore; 3.Shandong Univ, Qianfoshan Hosp, Dept Gen Surg, Jinan 250014, Peoples R China; 4.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 5.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 6.Univ Auckland, Dept Mol Med & Pathol, Auckland 1, New Zealand; 7.Univ New S Wales, Dept Pharmacol, Sydney, NSW 2052, Australia 8.Hubrecht Inst Dev Biol & Stem Cell Res, Utrecht, Netherlands; 9.Univ Auckland, Sch Biol Sci, Auckland 1, New Zealand; |
| 推荐引用方式 GB/T 7714 | Smith, G. C.,Zhang, Z. Y.,Mulvey, T.,et al. Clozapine directly increases insulin and glucagon secretion from islets: Implications for impairment of glucose tolerance[J]. SCHIZOPHRENIA RESEARCH,2014,157(1-3):128-133. |
| APA | Smith, G. C..,Zhang, Z. Y..,Mulvey, T..,Petersend, N..,Lach, S..,...&Shepherd, P. R..(2014).Clozapine directly increases insulin and glucagon secretion from islets: Implications for impairment of glucose tolerance.SCHIZOPHRENIA RESEARCH,157(1-3),128-133. |
| MLA | Smith, G. C.,et al."Clozapine directly increases insulin and glucagon secretion from islets: Implications for impairment of glucose tolerance".SCHIZOPHRENIA RESEARCH 157.1-3(2014):128-133. |
入库方式： OAI收割
来源：上海药物研究所
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