DC12
ADP ribosylation as a novel mechanism to regulate skeletal muscle insulin action
Background: Recent advances in mass spectrometry-based proteomics have enabled cell-wide identification of specific NAD-dependent ADP ribosylation on proteins that play important roles for cellular function. In animal models, our preliminary data suggest that insulin resistance is associated with marked differences in skeletal muscle ADP ribosylation status on protein involved in insulin action. This indicates a yet unrecognized interplay between insulin signaling and cellular NAD+ metabolism that regulates insulin sensitivity.
Objectives: (1) Define the global ADP ribosylome in insulin sensitive and resistant skeletal muscle from mice and humans. (2) Define the role of specific ADPr sites in mouse and human muscle cells in vitro for regulating insulin action. (3) Determine the interaction between ADP ribosylation and HubMOLs for mediating effects of insulin in skeletal muscle cells.