APLNR and Hyperglycemia: Although we clearly indicated that targeting APJ using various methods including shRNA, ML221, or dominant negative forms of APLN significantly rescued the effect of excessive APLN, we could only partially restore the expression of cell junction genes under hyperglycemia conditions, suggesting that high glucose might induce BTB damage via other factors, albeit we proved that high glucose could directly upregulate APLN expression in TM4 cells.