{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:42:24Z","timestamp":1788792144186,"version":"build-2803163510"},"reference-count":53,"publisher":"Canadian Science Publishing","issue":"6","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Psychiatry Neurosci"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p> Insulin receptors are widely expressed in the brain and may represent a crossroad between metabolic and cognitive disorders. Although antipsychotics, such as olanzapine, are the cornerstone treatment for schizophrenia, they are associated with high rates of type 2 diabetes and lack efficacy for illness-related cognitive deficits. Historically, this risk of diabetes was attributed to the weight gain propensity of antipsychotics, but recent work suggests antipsychotics can have weight-independent diabetogenic effects involving unknown brain-mediated mechanisms. Here, we examined whether antipsychotics disrupt central insulin action, hypothesizing that olanzapine would impair the well-established ability of central insulin to supress hepatic glucose production. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p> Pancreatic euglycemic clamps were used to measure glucose kinetics alongside a central infusion of insulin or vehicle into the third ventricle. Male rats were pretreated with olanzapine or vehicle per our established model of acute olanzapine-induced peripheral insulin resistance. Groups included (central\u2013peripheral) vehicle\u2013vehicle ( n = 11), insulin\u2013vehicle ( n = 10), insulin\u2013olanzapine ( n = 10) and vehicle\u2013olanzapine ( n = 8). <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> There were no differences in peripheral glucose or insulin levels. Unexpectedly, we showed that central insulin increased glucose uptake, and this effect was not perturbed by olanzapine. We replicated suppression of glucose production by insulin (clamp relative to basal: 77.9% \u00b1 13.1%, all p &lt; 0.05), an effect abolished by olanzapine (insulin\u2013olanzapine: 7.7% \u00b1 14%). <\/jats:p><\/jats:sec><jats:sec><jats:title>Limitations:<\/jats:title><jats:p> This study used only male rats and an acute dose of olanzapine. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p> To our knowledge, this is the first study suggesting olanzapine may impair central insulin sensing, elucidating a potential mechanism of antipsychotic-induced diabetes and opening avenues of investigation related to domains of schizophrenia psychopathology. <\/jats:p><\/jats:sec>","DOI":"10.1503\/jpn.170092","type":"journal-article","created":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T09:39:42Z","timestamp":1509356382000},"page":"424-431","source":"Crossref","is-referenced-by-count":39,"title":["In male rats, the ability of central insulin to suppress glucose production is impaired by olanzapine, whereas glucose uptake is left intact"],"prefix":"10.1139","volume":"42","author":[{"given":"Chantel","family":"Kowalchuk","sequence":"first","affiliation":[{"name":"From the Centre for Addiction and Mental Health, Toronto, Ont., Canada"},{"name":"the Institute of Medical Sciences, University of Toronto, Toronto, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Teo","sequence":"additional","affiliation":[{"name":"From the Centre for Addiction and Mental Health, Toronto, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Wilson","sequence":"additional","affiliation":[{"name":"From the Centre for Addiction and Mental Health, Toronto, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Araba","family":"Chintoh","sequence":"additional","affiliation":[{"name":"From the Centre for Addiction and Mental Health, Toronto, Ont., Canada"},{"name":"the Department of Psychiatry, University of Toronto, Toronto, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loretta","family":"Lam","sequence":"additional","affiliation":[{"name":"and the Department of Physiology, University of Toronto, Toronto, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sri Mahavir","family":"Agarwal","sequence":"additional","affiliation":[{"name":"From the Centre for Addiction and Mental Health, Toronto, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adria","family":"Giacca","sequence":"additional","affiliation":[{"name":"the Institute of Medical Sciences, University of Toronto, Toronto, Ont., Canada"},{"name":"and the Department of Physiology, University of Toronto, Toronto, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary J.","family":"Remington","sequence":"additional","affiliation":[{"name":"From the Centre for Addiction and Mental Health, Toronto, Ont., Canada"},{"name":"the Institute of Medical Sciences, University of Toronto, Toronto, Ont., Canada"},{"name":"the Department of Psychiatry, University of Toronto, Toronto, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret K.","family":"Hahn","sequence":"additional","affiliation":[{"name":"From the Centre for Addiction and Mental Health, Toronto, Ont., Canada"},{"name":"the Institute of Medical Sciences, University of Toronto, Toronto, Ont., Canada"},{"name":"the Department of Psychiatry, University of Toronto, Toronto, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"b1-42-6-424\/b1-42-6-424_1","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1001\/archpsyc.63.6.679","volume":"63","author":"Olfson M","year":"2006","journal-title":"Arch Gen Psychiatry"},{"key":"b2-42-6-424\/b2-42-6-424_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s40266-014-0152-x","volume":"31","author":"Guenette MD","year":"2014","journal-title":"Drugs Aging"},{"key":"b3-42-6-424\/b3-42-6-424_1","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1089\/cap.2010.0145","volume":"21","author":"Pringsheim T","year":"2011","journal-title":"J Child Adolesc Psychopharmacol"},{"key":"b4-42-6-424\/b4-42-6-424_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/j.2051-5545.2008.tb00154.x","volume":"7","author":"U\u00e7ok A","year":"2008","journal-title":"World Psychiatry"},{"key":"b5-42-6-424\/b5-42-6-424_1","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1124\/pr.107.00107","volume":"60","author":"Lieberman JA","year":"2008","journal-title":"Pharmacol Rev"},{"key":"b6-42-6-424\/b6-42-6-424_1","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1056\/NEJMoa051688","volume":"353","author":"Lieberman JA","year":"2005","journal-title":"N Engl J Med"},{"key":"b7-42-6-424\/b7-42-6-424_1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.diabet.2008.03.003","volume":"34","author":"Oriot P","year":"2008","journal-title":"Diabetes Metab"},{"key":"b8-42-6-424\/b8-42-6-424_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1001\/jamapsychiatry.2015.2923","volume":"73","author":"Galling B","year":"2016","journal-title":"JAMA Psychiatry"},{"key":"b9-42-6-424\/b9-42-6-424_1","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.ahj.2005.02.007","volume":"150","author":"Hennekens CH","year":"2005","journal-title":"Am Heart J"},{"key":"b10-42-6-424\/b10-42-6-424_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.schres.2008.12.012","volume":"108","author":"Chintoh AF","year":"2009","journal-title":"Schizophr Res"},{"key":"b11-42-6-424\/b11-42-6-424_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/sj.npp.1301209","volume":"32","author":"Houseknecht KL","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"b12-42-6-424\/b12-42-6-424_1","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.2337\/db10-0449","volume":"59","author":"Martins PJF","year":"2010","journal-title":"Diabetes"},{"key":"b13-42-6-424\/b13-42-6-424_1","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1007\/s00125-008-1152-3","volume":"51","author":"Smith GC","year":"2008","journal-title":"Diabetologia"},{"key":"b14-42-6-424\/b14-42-6-424_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1097\/JCP.0b013e318184b4c5","volume":"28","author":"Chintoh AF","year":"2008","journal-title":"J Clin Psychopharmacol"},{"key":"b15-42-6-424\/b15-42-6-424_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1210\/jc.2008-1815","volume":"95","author":"Vidarsdottir S","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"b16-42-6-424\/b16-42-6-424_1","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1097\/JCP.0b013e31829e8333","volume":"33","author":"Hahn MK","year":"2013","journal-title":"J Clin Psychopharmacol"},{"key":"b17-42-6-424\/b17-42-6-424_1","doi-asserted-by":"crossref","first-page":"3232","DOI":"10.2337\/db13-0430","volume":"62","author":"Teff KL","year":"2013","journal-title":"Diabetes"},{"key":"b18-42-6-424\/b18-42-6-424_1","doi-asserted-by":"crossref","unstructured":"VestriHSMaianuLMoelleringDR.Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis2007;32:765\u201372.","DOI":"10.1038\/sj.npp.1301142"},{"key":"b19-42-6-424\/b19-42-6-424_1","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/sj.mp.4001729","volume":"10","author":"Engl J","year":"2005","journal-title":"Mol Psychiatry"},{"key":"b20-42-6-424\/b20-42-6-424_1","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.2337\/diabetes.54.5.1264","volume":"54","author":"Porte D","year":"2005","journal-title":"Diabetes"},{"key":"b21-42-6-424\/b21-42-6-424_1","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/S0149-7634(00)00040-3","volume":"24","author":"Schulingkamp R","year":"2000","journal-title":"Neurosci Biobehav Rev"},{"key":"b22-42-6-424\/b22-42-6-424_1","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/mp.2008.40","volume":"13","author":"Girgis RR","year":"2008","journal-title":"Mol Psychiatry"},{"key":"b23-42-6-424\/b23-42-6-424_1","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/nm1202-798","volume":"8","author":"Obici S","year":"2002","journal-title":"Nat Med"},{"key":"b24-42-6-424\/b24-42-6-424_1","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.cmet.2012.09.005","volume":"16","author":"Filippi BM","year":"2012","journal-title":"Cell Metab"},{"key":"b25-42-6-424\/b25-42-6-424_1","doi-asserted-by":"crossref","first-page":"766","DOI":"10.2337\/db14-0685","volume":"64","author":"Dash S","year":"2015","journal-title":"Diabetes"},{"key":"b26-42-6-424\/b26-42-6-424_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.2337\/diacare.15.3.430","volume":"15","author":"Consoli A","year":"1992","journal-title":"Diabetes Care"},{"key":"b27-42-6-424\/b27-42-6-424_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.euroneuro.2013.07.011","volume":"24","author":"Hahn MK","year":"2014","journal-title":"Eur Neuropsychopharmacol"},{"key":"b28-42-6-424\/b28-42-6-424_1","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1111\/dom.12148","volume":"15","author":"Ikegami M","year":"2013","journal-title":"Diabetes Obes Metab"},{"key":"b29-42-6-424\/b29-42-6-424_1","doi-asserted-by":"crossref","unstructured":"KlingermanCMStipanovicMEHajnalA.Acute metabolic effects of olanzapine depend on dose and injection site2015;13:1559325815618915","DOI":"10.1177\/1559325815618915"},{"key":"b30-42-6-424\/b30-42-6-424_1","doi-asserted-by":"crossref","first-page":"862","DOI":"10.2337\/diabetes.54.3.862","volume":"54","author":"Ader M","year":"2005","journal-title":"Diabetes"},{"key":"b31-42-6-424\/b31-42-6-424_1","doi-asserted-by":"crossref","first-page":"914","DOI":"10.2337\/diab.36.8.914","volume":"36","author":"Finegood DT","year":"1987","journal-title":"Diabetes"},{"key":"b32-42-6-424\/b32-42-6-424_1","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/nature03439","volume":"434","author":"Pocai A","year":"2005","journal-title":"Nature"},{"key":"b33-42-6-424\/b33-42-6-424_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/mp.2010.33","volume":"16","author":"Albaugh VL","year":"2011","journal-title":"Mol Psychiatry"},{"key":"b34-42-6-424\/b34-42-6-424_1","doi-asserted-by":"crossref","first-page":"e43244","DOI":"10.1371\/journal.pone.0043244","volume":"7","author":"Girault EM","year":"2012","journal-title":"PLoS ONE"},{"key":"b35-42-6-424\/b35-42-6-424_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nature02440","volume":"428","author":"Minokoshi Y","year":"2004","journal-title":"Nature"},{"key":"b36-42-6-424\/b36-42-6-424_1","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.2337\/db10-0221","volume":"59","author":"Yang CS","year":"2010","journal-title":"Diabetes"},{"key":"b37-42-6-424\/b37-42-6-424_1","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ejphar.2013.08.006","volume":"718","author":"Ikegami M","year":"2013","journal-title":"Eur J Pharmacol"},{"key":"b38-42-6-424\/b38-42-6-424_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0006-8993(97)00963-3","volume":"777","author":"Wang J","year":"1997","journal-title":"Brain Res"},{"key":"b39-42-6-424\/b39-42-6-424_1","doi-asserted-by":"crossref","first-page":"5718","DOI":"10.1210\/endo.136.12.7588328","volume":"136","author":"Sahu A","year":"1995","journal-title":"Endocrinology"},{"key":"b40-42-6-424\/b40-42-6-424_1","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.cmet.2007.05.004","volume":"5","author":"K\u00f6nner AC","year":"2007","journal-title":"Cell Metab"},{"key":"b41-42-6-424\/b41-42-6-424_1","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.2337\/diabetes.53.10.2529","volume":"53","author":"van den Hoek AM","year":"2004","journal-title":"Diabetes"},{"key":"b42-42-6-424\/b42-42-6-424_1","first-page":"1163","volume":"13","author":"Mauri MC","year":"2014","journal-title":"EXCLI J"},{"key":"b43-42-6-424\/b43-42-6-424_1","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.2337\/db12-1701","volume":"62","author":"Kimura K","year":"2013","journal-title":"Diabetes"},{"key":"b44-42-6-424\/b44-42-6-424_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.cmet.2007.10.008","volume":"6","author":"Zhou L","year":"2007","journal-title":"Cell Metab"},{"key":"b45-42-6-424\/b45-42-6-424_1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.2337\/dc11-0064","volume":"34","author":"DeFronzo RA","year":"2011","journal-title":"Diabetes Care"},{"key":"b46-42-6-424\/b46-42-6-424_1","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/j.neuropharm.2011.02.019","volume":"62","author":"Boyda HN","year":"2012","journal-title":"Neuropharmacology"},{"key":"b47-42-6-424\/b47-42-6-424_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1017\/S1461145713000795","volume":"17","author":"Boyda HN","year":"2014","journal-title":"Int J Neuropsychopharmacol"},{"key":"b48-42-6-424\/b48-42-6-424_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1515\/JPEM.2003.16.1.5","volume":"16","author":"Kaiser N","year":"2003","journal-title":"J Pediatr Endocrinol Metab"},{"key":"b49-42-6-424\/b49-42-6-424_1","doi-asserted-by":"crossref","DOI":"10.1177\/0269881105056641","volume":"19","author":"Best L","year":"2005","journal-title":"J Psychopharmacol"},{"key":"b50-42-6-424\/b50-42-6-424_1","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1037\/0894-4105.12.3.426","volume":"12","author":"Heinrichs RW","year":"1998","journal-title":"Neuropsychology"},{"key":"b51-42-6-424\/b51-42-6-424_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/acps.12374","volume":"131","author":"Nielsen RE","year":"2015","journal-title":"Acta Psychiatr Scand"},{"key":"b52-42-6-424\/b52-42-6-424_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.schres.2013.01.034","volume":"146","author":"Li J","year":"2013","journal-title":"Schizophr Res"},{"key":"b53-42-6-424\/b53-42-6-424_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/JCP.0b013e31820ebd0e","volume":"31","author":"Fan X","year":"2011","journal-title":"J Clin Psychopharmacol"}],"container-title":["Journal of Psychiatry and Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdnsciencepub.com\/doi\/full-xml\/10.1503\/jpn.170092","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdnsciencepub.com\/doi\/pdf\/10.1503\/jpn.170092","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T16:31:09Z","timestamp":1756830669000},"score":1,"resource":{"primary":{"URL":"https:\/\/cdnsciencepub.com\/doi\/10.1503\/jpn.170092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1503\/jpn.170092"],"URL":"https:\/\/doi.org\/10.1503\/jpn.170092","relation":{},"ISSN":["1180-4882","1488-2434"],"issn-type":[{"value":"1180-4882","type":"print"},{"value":"1488-2434","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11]]}}}