Mechanisms of RSV-targeted SIRTs in the regulation of type 2 diabetes mellitus.
| RSV-targeted SIRTS | Mechanisms of action | Regulation of substrates and pathways | Roles in diseases | Research objects | References |
|---|---|---|---|---|---|
| SIRT1 | ↑NAD+/NADH↓UCP2 | RSV, increasing NAD/NADH ratio and further regulating the SIRT1/UCP2 axis, protects β-cells against ethanol-induced dysfunction. | Protects β-cell function under ethanol exposure. | Rat insulinoma INS-1 cells | [55] |
| SIRT1 | ↓FOXO1↓NF-κB | SIRT1 via deacetylating FOXO1 and the NF-κB subunit p65 represses oxidative stress-induced hyperglycemia. | Overexpression of SIRT1 prevents cytokine toxicity and maintains normal insulin-secreting responses to glucose. | RINm5F cells and rat islets | [59] |
| SIRT1 | ↑AMPK↑PGC-1α↑SOD1↑SOD2 | RSV treatment increased the AMPK and SIRT1 and decreased PI3K-Akt signaling to improve diabetes-induced renal damage. | Reduce renal cell death and oxidative stress induced by type 2 diabetes mellitus. | C57BLKS/J db/m and db/db mice | [57] |
| SIRT3 | ↑SIRT3↑TFAM↑ATP↓TGF-β/Smad | RSV activates SIRT3, SIRT3 indirectly affects glucose metabolism by decreasing the acetylation status of TFAM, maintaining the stability of mitochondrial function. | Regulates the acetylation status of TFAM and preserves the mitochondrial function along with cellular size in the diabetic rat heart. | Rat-cardiomyoblast cells (H9C2) | [58] |
Akt: protein kinase B; AMPK: AMP-activated protein kinase; FOXO1: forkhead box O1; NADH: nicotinamide adenine dinucleotide; NF-κB: nuclear factor kappa-B; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PI3K: phosphatidylinositol 3-kinase; RSV: resveratrol; SIRT: sirtuin; Smad: Sma- and mad-related protein; SOD: superoxide dismutase; TFAM: mitochondrial transcription factor A; TGF-β: transforming growth factor-β; UCP: uncoupling protein.
JY: Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review & editing. SC: Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review & editing. TZ: Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review & editing. YZ: Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review & editing. ZL: Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review & editing. HL: Conceptualization, Investigation, Writing—review & editing, Supervision. All authors read and approved the submitted version.
The authors declare that there are no conflicts of interest.
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This work was supported by a grant from the Natural Science Foundation of Shandong Province, China [No. ZR2025MS387]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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