Genetic disruption of the cardiomyocyte circadian clock differentially influences insulin-mediated processes in the heart

Genetic disruption of the circadian clock in specific heart cells led to altered insulin signaling and increased activation of the Akt pathway.

• Disruption of the circadian clock in heart cells changed the expression of several components involved in insulin signaling.
• Baseline and insulin-mediated activation of the Akt protein was increased in hearts with disrupted circadian clocks.
• Insulin-mediated glucose utilization was reduced in genetically modified hearts, potentially due to decreased levels of Inhibitor-1.
• Increased Akt activation was linked to persistent activation of mTOR signaling, which affected processes like protein synthesis and cell growth.
• Treatment with rapamycin normalized heart size in mice with disrupted circadian clocks, indicating a potential therapeutic approach.

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