title: Estrogen replacement reverses olanzapine-induced weight gain and hepatic insulin resistance in ovariectomized diabetic rats.
abstract: OBJECTIVE
  We investigated whether estrogen replacement modulated energy and glucose metabolic changes induced by olanzapine (OZP) and risperidone (RPD) in 90% pancreatectomized diabetic rats, some of whom had also been ovariectomized (OVX) and some of whom had not (sham).
  
  
  METHODS
  OVX diabetic rats were subcutaneously injected with estrogen replacement (17beta-estradiol, 30 microg/kg/day) or a vehicle. Each group was divided into 3 subgroups, and each subgroup was orally either given a placebo, RPD (0.5 mg/kg body weight/day) or OZP (2 mg/kg body weight/day) for 8 weeks. Sham rats were also divided into 3 subgroups and given drugs in the same manner as the OVX rats were. All rats were fed high-fat diets.
  
  
  RESULTS
  OZP increased body weight and epididymal fat pads more than the control (vehicle) in sham and OVX rats. Increased body weight in OZP-treated sham and OVX rats was due to the increment in food intake, which was associated with potentiating the phosphorylation of hypothalamic adenosine-monophosphate-activated protein kinase. At euglycemic hyperinsulinemic clamping, OZP decreased glucose infusion rates and increased hepatic glucose output in OVX diabetic rats. In sham rats, OZP increased hepatic glucose output but not as much as in OVX rats. Hepatic insulin signaling and glucose sensing were attenuated in OZP-treated OVX rats, and the attenuation increased hepatic phosphoenolpyruvate carboxykinase expression to induce gluconeogenesis. These negative and harmful effects noted among OZP-treated OVX rats were reversed by estrogen replacement treatment. However, RPD did not alter body weight and peripheral insulin sensitivity in sham and OVX rats.
  
  
  CONCLUSIONS
  OZP treatment should be avoided when treating diabetic and schizophrenic women, especially those in their postmenopausal period.
authors.affiliation: Department of Food and Nutrition, Diabetes/Obesity Center, College of Natural Science, Hoseo University, Asan, South Korea. smpark @ hoseo.edu
authors.forename: Sunmin
authors.initials: S
authors.lastname: Park
authors.forename: Sang Mee
authors.initials: SM
authors.lastname: Hong
authors.forename: I L Sung
authors.initials: IL
authors.lastname: Ahn
authors.forename: Da Sol
authors.initials: DS
authors.lastname: Kim
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000494:pharmacology; D001569:Benzodiazepines / Q000009:adverse effects* / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004435:Eating / Q000187:drug effects; D004958:Estradiol / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000077152:Olanzapine; D010052:Ovariectomy; D010180:Pancreatectomy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000009:adverse effects / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D004958:Estradiol; D005947:Glucose; D018967:Risperidone; D000077152:Olanzapine