GRK2 and Insulin resistance: For example, up-regulation of G protein-coupled receptor kinase 2 (GRK-2) with DM or high-fat feeding inhibits GPCR and InsR signaling, promoting further lipid accumulation, insulin-resistance and hypertrophy [182], with recent evidence these changes in GRK-2 also inhibits cardioprotective opioid receptor signaling [183].