? Insulin conserves glucose while insulin resistance reduces the conservation of glucose. Insulin resistance is associated with many health complications. Many people with insulin resistance develop diabetes. For unknown reasons, insulin resistance also promotes heart disease and breast cancer. Liver insulin resistance increases in the obese state partly because the expansion of fat tissue leads to a low level of adiponectin in the circulation. We are investigating the adiponectin pathway that increases insulin sensitivity in the liver. Our specific goals are to determine the role of (1) mTOR, a potential target of adiponectin and an insulin signaling intermediate that inhibits glucose production, (2) AMPK, a target of adiponectin that inhibits glucose production, (3) lysosome activity, a cellular process of protein degradation that produces amino acids used in gluconeogenesis and (4) the TCA cycle, a major gluconeogenic pathway that uses amino acids for glucose production. The insight we gain could lead to a better understanding of adiponectin action in the liver and more effective interventions for the treatment of insulin resistance. ? ?
