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Updated: May 3, 2026

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
Published on: May 16, 2021
The AMPK-SIRT signaling network regulates glucose tolerance under calorie restriction conditions
M F P Silvestre1, B Viollet2, P W Caton3
1Barts and the London, School of Medicine and Dentistry, Queen Mary University of London, London, UK; Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
Aims:
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.
Main Methods:
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).
Key Findings:
CR-AMPKα1/2(-/-) displayed impaired glucose tolerance (*p<0.05), in association with down-regulated SIRT1 and PGC-1α expression (<300% vs. CR-WT, (±±)p<0.01). Moreover, AMPK activity was decreased following SIRT1 inhibition in L6 cells (~0.5-fold vs. control, *p<0.05).
Significance:
This study demonstrates that skeletal muscle-specific AMPK deficiency impairs the beneficial effects of CR on glucose tolerance and that these effects may be dependent on reduced SIRT1 levels.
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