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AICAR Prevents Acute Olanzapine-Induced Disturbances in Glucose Homeostasis

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dc.contributor.advisor Wright, David C. Bush, Natasha Dawn 2018-03-28T13:04:01Z 2018-03-28T13:04:01Z 2018-03 2018-03-16 2018-03-28
dc.description.abstract The purpose of this thesis was to examine whether the 5’AMP-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) could prevent acute olanzapine (OLZ)-induced metabolic disturbances in mice. Experiments were performed using male C57BL6/J mice separated into four treatment groups: A) Vehicle; B) Vehicle + OLZ (5mg/kg; IP); C) Vehicle + AICAR (250mg/kg; IP); or D) AICAR + OLZ. OLZ rapidly increased blood glucose, reduced the insulin response and increased pyruvate intolerance, all of which were prevented with AICAR. These results were reproduced in high-fat diet-induced obese mice. While OLZ significantly reduced the respiratory exchange ratio (RER), VO2, activity and heat production, AICAR had no effect on these parameters. Peripheral injection of AICAR, but not OLZ, activated AMPK signalling in the hypothalamus. Despite increasing hypothalamic AMPK signalling, this study provides evidence that AICAR prevents OLZ-induced hyperglycemia perhaps by preventing the development of insulin resistance and by reducing liver glucose production. en_US
dc.description.sponsorship Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Ontario Graduate Scholarship en_US
dc.language.iso en en_US
dc.subject Metabolism en_US
dc.subject AMP-dependent protein kinase (AMPK) en_US
dc.subject Schizophrenia en_US
dc.subject Olanzapine en_US
dc.subject Antipsychotics en_US
dc.subject Glucose Homeostasis en_US
dc.subject Mouse Model en_US
dc.subject AICAR en_US
dc.title AICAR Prevents Acute Olanzapine-Induced Disturbances in Glucose Homeostasis en_US
dc.type Thesis en_US Human Health and Nutritional Sciences en_US Master of Science en_US Department of Human Health and Nutritional Sciences en_US
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