Figure 2.

SIRT1 antagonizes oxidative stress in diabetic vascular complications. SIRT1 directly or cooperatively with AMPK to activate various downstream effectors, including PGC1α, FOXOs, and PPARα. SIRT1 also stimulate eNOS and inhibit NOX and mTOR to trigger anti-oxidant protective response. In addition, H₂S can either activate SIRT1 directly via sulfydration, or indirectly via increasing NAD+ level. Furthermore, several miRNAs, such as miR-34a, miR-200c, and miR-23a, directly inhibit the mRNA expression of sirt1 in DM, while other miRNAs including miR-126 promote sirt1 expression indirectly with unclear mechanism.