Factors influencing glucose homeostasis in a rat model with mutated ATP synthase

• Author / Creator

  Harasym, Anne C.

• This study examined glucose homeostasis mechanisms involved in the BHE/cdb rat model of mitochondrial diabetes with a mutated Fo subunit of ATP synthase. Twenty-one-week old male BHE/cdb rats exhibited enhanced glucose tolerance despite impaired insulin secretion. Whole body in vivo characterization showed that BHE/cdb rats had enhanced insulin sensitivity compared to controls, along with moderately increased (p<0.01) respiratory exchange ratios, oxygen consumption, carbon dioxide production and heat production, despite similar relative body composition, physical activity, food and water consumption. In vitro markers of insulin-dependent and insulin-independent signaling pathways were similar in BHE/cdb rats and controls. Phosphoenolpyruvate carboxykinase expression in liver (p<0.05), liver glycogen storage (p<0.05), and epitrochlearis muscle glycogen (p<0.01) were increased in BHE/cdb rats. Additionally, in vivo pyruvate-stimulated gluconeogenesis was attenuated in BHE/cdb rats (p<0.01). Results indicate that increased glucose oxidation, increased thermogenesis, and reduced hepatic glucose output mediate glucose tolerance in the BHE/cdb model.

• Subjects / Keywords

  • BHE/cdb
  • Gluconeogenesis
  • Mitochondrial diabetes
  • Glucose tolerance

• Graduation date

  Spring 2012

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R31P7Q

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.