THE ROLE OF ANKRD2 IN INSULIN SENSITIVITY
Nhu Y Doan, Angelina Hernandez-Carretero, Olivia Osborn, Natalie Weber.
University of California, San Diego, La Jolla, CA.
Insulin resistance is a characteristic feature of type-2 diabetes and plays a major role in the pathogenesis of the disease. Insulin resistance is defined as a reduced response of target tissues such as the skeletal muscle, liver, and adipocytes, to insulin. Skeletal muscle is the major site of glucose uptake in the postprandial state in humans. In this study we used RNA-seq to discover gene expression changes in mouse muscle in obesity and diabetes using lean, low fat (LF) fed mice and obese/diabetic, high fat (HF) diet fed mice. We found that expression of ankyrin repeat domain protein 2 (Ankrd2) was reduced in muscle from HF mice compared with LF diet fed mice. We hypothesized that Ankrd2 contributes to insulin sensitivity in the muscle and that reduction of Ankrd2 may impair insulin-stimulated glucose uptake. We used siRNA-mediated knockdown of Ankrd2 in rat L6 myotube cells and performed glucose uptake assays. Preliminary results show that approximately 75% knockdown of Ankrd2 expression impairs insulin-stimulated glucose uptake by 1.5-fold. This study will determine whether Ankrd2 is a useful therapeutic target to enhance the insulin sensitivity of obese and diabetic individuals.