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Summary of the new mechanistic findings of the present study. NO stimulates S-nitrosylation of PTP1B, which decreases its enzymatic activity, thereby limiting the dephosphorylation of tyrosine residues on key insulin signaling proteins (IR, IRS1/2, and Src), which facilitates insulin TET (42). Txnip promotes NO-mediated S-nitrosylation of PTP1B through inhibition of denitrosylases, leading to the inhibition of PTP1B and activation of insulin signaling. pY, tyrosine phosphorylation.
