Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells

Abstract

We examined in HepG2 cells whether glucose-induced changes in AMP-activated protein kinase (AMPK) activity could be mediated by SIRT1, an NAD-dependent histone/protein deacetylase that has been linked to the increase in longevity caused by caloric restriction. Incubation with 25 vs. 5 mM glucose for 6 h concurrently diminished the phosphorylation of AMPK (Thr 172) and ACC (Ser 79), increased lactate release, and decreased the abundance and activity of SIRT1. In contrast, incubation with pyruvate (0.1 and 1 mM) for 2 h increased AMPK phosphorylation and SIRT1 abundance and activity. The putative SIRT1 activators resveratrol and quercetin also increased AMPK phosphorylation. None of the tested compounds (low or high glucose, pyruvate, and resveratrol) significantly altered the AMP/ATP ratio. Collectively, these findings raise the possibility that glucose-induced changes in AMPK are linked to alterations in SIRT1 abundance and activity and possibly cellular redox state.

Supplementation of pyruvate prevents palmitate-induced impairment of glucose uptake in C2 myotubes

“…The protective roles of FAO stimulators and TCA cycle substrates in PIIGU also suggest that the restoration of mitochondrial oxidative metabolism may protect against insulin resistance in palmitate-treated cells. A report suggesting that pyruvate can augment mitochondrial biogenesis (Suchankova et al, 2009;Wilson et al, 2007) supports the hypothesis that supplementation with pyruvate can prevent PIIR through enhanced mitochondrial metabolism. The role of appropriate mitochondrial metabolism in insulin-stimulated glucose uptake is also supported by recent reports showing enhanced glucose uptake as a result of increased TCA cycle flux induced by treatment with the anaplerotic amino acid glutamine or the pyruvate dehydrogenase activator dichloroacetate (Koves et al, 2008;Philp et al, 2010;Thyfault et al, 2007).…”

Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target

“…46,47 However, serum glucose levels were not examined in this study. SIRT1 was previously reported to be involved in glucose metabolism due to the activation of AMPK (5' adenosine monophosphate-activated protein kinase), 48 and also contributed to the regulation of serum glucose levels in type 2 diabetes mellitus. 49 Therefore, further studies are needed to clarify the adverse effects associated with the administration of EX527, especially regarding metabolic disorders.…”

Exercise training enhanced SIRT1 longevity signaling replaces the IGF1 survival pathway to attenuate aging-induced rat heart apoptosis

“…Exercise training will activate the muscle cells of the AMP-activated protein kinase (AMPK), and AMPK will further promote downstream pathways of SIRT1 and peroxisome-proliferator-activated receptor coactivators (PGC-1α) (Suchankova et al 2009). PGC-1α effects glucose transport regulation and mitochondrial biogenesis (Jäger et al 2007;Lagouge et al 2006).…”