I am interested in the regulation of insulin action, insulin secretion and β cell mass by leucine, KIC, and mTOR. Over-nutrition due to an abundant food supply significantly contributes to the obesity and diabetes epidemics in humans. Nutrients acting as direct signals and stimulators of insulin secretion activate the mTOR signaling pathway. mTOR is a master regulator of cell growth, protein synthesis, and energy metabolism, thereby playing important roles in diabetes, obesity, cancer, and aging. Over-activation of mTOR signaling leads to insulin resistance through a negative feedback mechanism of down-regulating insulin signaling. Leucine is the most potent nutrient signal activating mTOR. My research lies on determining the effects of mTOR activation interacted with leucine and insulin on insulin actions in muscle, liver, and is β cells. We are currently working on four projects. Project 1 is to determine the metabolic and molecular mechanisms by which insulin sensitivity and glucose tolerance is markedly improved in mice lacking mitochondrial branched-chain aminotransferase βBCATm), which catalyzes the first step of leucine catabolism. Project 2 is to determine the mechanisms underlying Α -ketoisocaproate βKIC) stimulated insulin secretion. Project 3 studies glucose metabolism and insulin secretion in a mouse model of MSUD βmaple syrup urine disease), E2 knockout mice in which the second step of BCAA metabolism is blocked and branched-chain keto-acids are accumulated. Project 4 is about skeletal muscle wasting, protein metabolism and related signaling pathways in the R6/2 mouse model of Huntington's disease. These studies use transgenic mouse models, in vivo physiology, in vitro biochemical and cell signaling approaches. The research will provide better understanding of pathogenesis and therapeutic strategies of type 2 diabetes.