title: Olanzapine effects on body composition, food preference, glucose metabolism and insulin sensitivity in the rat.
abstract: The atypical antipsychotic drug olanzapine induces weight gain and defects in glucose metabolism in patients. Using a rat model we investigated the effects of acute and long term olanzapine treatment on weight gain, food preference and glucose metabolism. Olanzapine treated rats fed a chow diet grew more slowly than vehicle controls but olanzapine treated animals fed a high fat/sugar diet grew faster than control animals on the same diet. These changes in weight were paralleled by changes in fat mass. Olanzapine also induced a strong preference for a high fat/high sugar diet. Acute exposure to olanzapine rapidly induced severe impairments of glucose tolerance and increased insulin secretion but did not impair insulin tolerance. These results indicate the defect in glucose metabolism induced by acute olanzapine treatment was most likely due to increased hepatic glucose output associated with a reduction in active GLP-1 levels and correspondingly high glucagon levels.
authors.affiliation: Department of Molecular Medicine and Pathology and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.
authors.forename: G C
authors.initials: GC
authors.lastname: Smith
authors.forename: M H
authors.initials: MH
authors.lastname: Vickers
authors.forename: P R
authors.initials: PR
authors.lastname: Shepherd
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001823:Body Composition / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects / Q000523:psychology; D005518:Food Preferences / Q000187:drug effects* / Q000523:psychology; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism; D000077152:Olanzapine; D051381:Rats; D012559:Schizophrenia / Q000188:drug therapy; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D007328:Insulin; D001569:Benzodiazepines; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose; D000077152:Olanzapine