CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice

Circadian misalignment may induce insulin resistance through the down-regulation of CLOCK and BMAL1 in skeletal muscle.

• CLOCK and BMAL1 are core circadian transcription factors that are down-regulated in insulin-resistant muscle cells.
• Insulin signaling is weakened in the skeletal muscle of mice lacking functional CLOCK.
• Knockdown of CLOCK or BMAL1 in muscle cells leads to insulin resistance.
• Introducing CLOCK and BMAL1 improves insulin sensitivity in muscle cells.
• CLOCK and BMAL1 influence the expression of sirtuin 1 (SIRT1), which is linked to insulin sensitivity.
• BMAL1 and SIRT1 levels decrease in mice kept in constant darkness, and resveratrol can enhance SIRT1 activity.

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