Novel role for adenosine kinase in the control of hepatic gluconeogenesis
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abstract
Diabetes is characterized by excessive sugar (glucose) in blood, which is termed as hyperglycemia. Many studies have demonstrated the liver as a main organ whose dysfunction causes hyperglycemia. Because of this, targeting the liver to reduce hyperglycemia is a viable approach for the treatment of diabetes. In the liver, adenosine kinase (ADK) is a maker that converts adenosine to adenosine-monophosphate. As a result, ADK critically controls the intracellular concentrations of adenosine and the related methionine cycle (pathways that alter methylation). However, the exact functions of the ADK in liver cells are nearly unknown. The Principal Investigator (PI) was previously supported by a bridging fund from American Diabetes Association, which enabled him to generate new compelling preliminary data to form this application. Of significance, the PI made several novel findings that link ADK to liver glucose production and whole body glucose homeostasis. Therefore, the goal of this project is to examine how the ADK in liver cells controls glucose production. Approaches involving novel mouse models and cultured cells will be used to explore the extent to which liver glucose production and blood sugar are influenced by altering ADK in the liver cells, and to understand how these changes are brought about. The successful completion of this project will provide new insights of how ADK serves as a determinant of liver glucose production. Additionally, this project will open up a new ADK inhibition-based direction for the treatment of diabetes.
