Minor amounts of glucose incorporated into the cells is metabolized via the hexosamine biosynthetic pathway, resulting in the production of uridine-5’-diphosphate-
N-acetylglucosamine (UDP-GlcNAc), which is utilized as a donor substrate for the
N- and
O-linked glycosylation of extracellular and membrane proteins in the Golgi apparatus, or for the
O-linked GlcNAc modification (
O-GlcNAcylation) of intracellular proteins in the cytosol. In particular,
O-GlcNAcylation, the addition of GlcNAc to serine/threonine residues, is reversibly regulated by the enzymatic activities of
O-GlcNAc transferase (OGT) and
O-GlcNAcase. Since OGT activity is sensitive to the intracellular UDP-GlcNAc level, flux via the hexosamine pathway influences
O-GlcNAcylation. Actually, excess flux via the hexosamine pathway and resultant increased
O-GlcNAcylation are associated with several pathophysiological conditions, including insulin resistance. To date, there are several studies addressing the effects of exercise on the hexosamine pathway and
O-GlcNAcylation. Thus, this short review focuses on the relationships among exercise, the hexosamine pathway,
O-GlcNAcylation, and insulin resistance.
View full abstract