TARGETING SIRTUIN 1 IN TYPE 2 DIABETES MELLITUS: A NOVEL APPROACH

Abstract Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disease defined by insulin resistance, hyperglycemia, and chronic inflammation. Sirtuin-1 (SIRT1), an NAD⁺-dependent acetylase, regulates the metabolism of glucose, lipids, mitochondrial function, and inflammatory processes. Activating SIRT1 strengthens the sensitivity of the body to insulin, accelerates the oxidation of fatty acids, and decreases hepatic steatosis. Both natural products like resveratrol, quercetin, and synthetic activators like SRT2104 effectively regulate the activity of SIRT1, although bioavailability and safety limitations exist. Circulating concentrations of SIRT1 are inversely correlated to glycemic and inflammatory indices, suggesting the latter as an acceptable indirect biomarker. Furthermore, the activation of pancreatic β-cells by SIRT1 shields these cells from oxidant and inflammatory injury, supporting the preservation of the secretion. Conclusion: SIRT1 represents a tri-functional target that integrates metabolic control, biomarker value, and therapeutic strategy in T2DM. Treatments that enhance SIRT1 activity by pharmacological, nutraceutical, or lifestyle interventions can maximize glycemic control, minimize complications, and allow precision medicine.