Fig. 2

Overview of sirtuins in glucose metabolism. Selected pathways in nucleus, cytosol and mitochondria are depicted. a Located in cytoplasm, SIRT2 deacetylates the rate-limiting enzyme PEPCK and promotes gluconeogenesis during low nutrient condition. Both SIRT3 and SIRT4 target GDH in mitochondria but their enzymatic activities seem to be opposite. Besides GDH, SIRT4 also reduces PDH activity which converts pyruvate to acetyl CoA. SIRT5 facilitates glycolysis via glycolytic enzyme GAPDH and may disrupt glutamine metabolism through GLS. b In respect to the nuclear sirtuins, both SIRT1 and SIRT6 suppress the transcription factor HIF1α through different manners and subsequently attenuate glycolysis. The reciprocal activation of FOXO1 and its coactivator PGC-1α by SIRT1 reinforces the gluconeogenic transcription. By contrast, SIRT6 down-regulates PGC-1α and suppresses hepatic glucose production. PEPCK,phosphoenolpyruvate carboxykinase; GDH,glutamate dehydrogenase; PDH,pyruvate dehydrogenase; GAPDH,glyceraldehyde phosphate dehydrogenase; GLS,glutaminase; PGC-1α,Peroxisome proliferator-activated receptor gamma coactivator 1 α; FOXO1,forkhead box protein O1