Particularly, as evidenced in preclinical studies, CHR seems to attenuate the diabetes-related tissue damage by ameliorating blood glucose levels, insulin resistance and inflammatory state in diabetic animals, by reducing Vascular Endothelial Growth Factor (VEGF) in preclinical models of diabetic retinopathy and by decreasing advanced glycosylation end products (AGEs), TGF-β1/Smad and Col-I deposition in diabetic hearts (Li et al., 2014; Farkhondeh et al., 2019; Zhou et al., 2021a; Salama et al., 2022). This evidence concerns the gene INS and diabetic retinopathy.