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Flavonoids derived from citrus fruits exhibit antioxidant properties that can enhance glycemic control and modulate signaling pathways related to insulin sensitivity and OS ( 4.6.5 SIRT1/PGC-1α pathway The Sirtuin 1/PPAR-γ co-activator1α (SIRT1/PGC-1α) pathway is critical in regulating mitochondrial function and OS, which are key factors in the pathogenesis of DN

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Surrounding fibroblasts and macrophages share with tumor cells the ability to release proteolytic enzymes, like metalloproteinases (MMPs), elastase and trypsin, which degrade extracellular matrix and cause abnormal blood vessel permeability [36,37,38]