Moreover, we show that the SENP1-VEGFR2 signalling is impaired under hyperglycemia in vitro and at diabetic settings in vivo; the reduction of the SENP1-VEGFR2 signalling account for the impaired angiogenesis in diabetes as overexpression of non-SUMOylated form of VEGFR2 could rescue the angiogenic defects in STZ mice. Here, KDR is linked to diabetes mellitus.