NAD+-sirtuins modulate glucose metabolism via HIF-1 in all metazoan species from the simplest animal Trichoplax adhaerens to human. Sirtuins (SIRT) consist of seven mammalian proteins, SIRTs 1–7. Some isoforms of sirtuins inhibit HIF-1 activation by deacetylation or noncatalyzing effects [34–38]. Under hypoxia or pseudohypoxia, decreased NAD+ levels downregulated SIRT, leading to upregulated HIF-1 activation which shift the glucose metabolism by promoting glycolysis and by inhibiting oxidative phosphorylation.
