FOXO1 and Hyperglycemia: Similarly to the results by Zheng et al. (see Section 4.4) [200], in a study on MMECs hyperglycemia has been proven to accelerate endothelial apoptosis and senescence via changes in SIRT1 expression and downstream signaling targets FoxO-1/p53, whereas metformin prevents these detrimental effects attenuating hyperglycemia-induced oxidative stress and upregulating SIRT1 expression [206].