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Schematic draw demonstrates that increased flux through the hexosamine biosynthetic pathway leads to enhanced O-GlcNAcylation of eNOS in condition of high glucose, which interferes with eNOS-Ser1177 phosphorylation by Akt to reduce histamine-induced, NO-dependent dilation of skeletal muscle arterioles. GFAT: glutamine fructose-6-phosphate amidotransferase, O-GlcNAc: O-linked attachment of N-acetyl-glucosamine, OGT: O-linked N-acetylglucosaminyl-transferase.
