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We previously showed that insulin triggers the epigenetic regulator DBC1 to prime SIRT1 for repression by the multifunctional trafficking protein PACS\u20102. Here, we show that liver DBC1\/PACS\u20102 regulates the diurnal inhibition of SIRT1, which is critically important for insulin\u2010dependent switch in fuel metabolism from fat to glucose oxidation. We present the x\u2010ray structure of the DBC1 S1\u2010like domain that binds SIRT1 and an NMR characterization of how the SIRT1 N\u2010terminal region engages DBC1. This interaction is inhibited by acetylation of K112 of DBC1 and stimulated by the insulin\u2010dependent phosphorylation of human SIRT1 at S162 and S172, catalyzed sequentially by CK2 and GSK3, resulting in the PACS\u20102\u2010dependent inhibition of nuclear SIRT1 enzymatic activity and translocation of the deacetylase in the cytoplasm. 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