Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance

Liver-specific deficiency of Sirt1 leads to chronic hyperglycemia and insulin resistance in mice.

• Sirt1 positively influences the expression of Rictor, which is part of a signaling pathway that regulates glucose production.
• Deficiency of Sirt1 results in increased hepatic glucose output and oxidative stress.
• The oxidative stress from Sirt1 deficiency disrupts mTOR complex 2 signaling, impacting insulin-sensitive organs.
• Insulin resistance observed in mice with Sirt1 deficiency could be partially reversed through antioxidant treatment.
• The findings suggest a potential role for antioxidants in mitigating insulin resistance, particularly as populations age.

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