The AMPK-SIRT signaling network regulates glucose tolerance under calorie restriction conditions

• Published in: Life sciences (1973) 2014-03, Vol.100 (1), p.55-60
• Main Authors: Silvestre, M.F.P., Viollet, B., Caton, P.W., Leclerc, J., Sakakibara, I., Foretz, M., Holness, M.C., Sugden, M.C.
• Format: Article
• Language: English
• Subjects: Acetylation; AMP protein kinase (AMPK); AMP-Activated Protein Kinases - deficiency; AMP-Activated Protein Kinases - genetics; Animals; Caloric Restriction; Calorie restriction; Cells, Cultured; Enzyme Repression; Female; Glucose; Glucose Intolerance; Insulin; Mice; Mice, Knockout; Muscle, Skeletal - enzymology; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; PGC-1α; Protein Processing, Post-Translational; Signal Transduction; SIRT1; Sirtuins - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2014.01.080

SIRT1 and AMP-activated protein kinase (AMPK) share common activators, actions and target molecules. Previous studies have suggested that a putative SIRT1-AMPK regulatory network could act as the prime initial sensor for calorie restriction-induced adaptations in skeletal muscle—the major site of insulin-stimulated glucose disposal. Our study aimed to investigate whether a feedback loop exists between AMPK and SIRT1 in skeletal muscle and how this may be involved glucose tolerance. To investigate this, we used skeletal muscle-specific AMPKα1/2 knockout mice (AMPKα1/2−/−) fed ad libitum (AL) or a 30% calorie restricted (CR) diet and L6 rat myoblasts incubated with SIRT1 inhibitor (EX527). CR-AMPKα1/2−/− displayed impaired glucose tolerance (*p