Representing a Novel Model of Diet-Induced, Inherited Insulin Resistance and Obesity, Atp10c Heterozygous Mice Show Alterations in Glucose Uptake via both Insulin-Dependent and Non-Dependent Pathways

Diet-Induced Obesity (DIO) is a major risk factor for a number of disorders including non-insulindependent Type 2 Diabetes Mellitus (T2D). In our novel mouse model, the gene Atp10c is a strong candidate for metabolic disorders of Insulin Resistance (IR) and DIO. As such, we hypothesized that ATP10C has a key role in glucose metabolism via insulin-dependent and independent signaling pathways. We first examined the expression of Atp10c in both a genetic as well as an environmental mouse model of obesity. While our results showed that there were no significant changes in Atp10c expression in the genetic and environmental mouse models, our data does show high expression of Atp10c in key peripheral tissues namely skeletal muscle and adipose depots. Next, we performed western immunoblot analysis to detect potential targets of ATP10C in both the phosphatidyinosital-3-kinase (PI3K) and the mitogenActivated Protein Kinase (MAPK) pathways. When accessing MAPK pathway proteins, the mutants showed a significant decrease in the ratio of activated to native forms of p38 and ERK1/2. Additionally, we observed differences in the PI3K pathway as there were significant results along with data from our investigations of skeletal muscle prove our hypothesis that Atp10c must play a role in glucose metabolism, and suggest that the action of Atp10c is potentially mediated via both the MAPK pathway as well as the PI3K pathway.