Main content

AICAR Prevents Acute Olanzapine-Induced Disturbances in Glucose Homeostasis

Show full item record

Title: AICAR Prevents Acute Olanzapine-Induced Disturbances in Glucose Homeostasis
Author: Bush, Natasha Dawn
Department: Department of Human Health and Nutritional Sciences
Program: Human Health and Nutritional Sciences
Advisor: Wright, David C.
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.
URI: http://hdl.handle.net/10214/12586
Date: 2018-03-28


Files in this item

Files Size Format View
Bush_Natasha_201803_MSc.pdf 3.817Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record