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

Abstract

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.