EFNA5 and Hyperglycemia: Hyperglycemia increases notch activity in vitro and vivo, and consistent activation of notch results in impaired GSIS and blocks maturation of β cells, which may be a result of degradation of MAFA due to the blockage of its binding to kat2b.162 In addition, activated notch may affect islet architecture through Ephrin A5 (EFNA5) which is increased in T2D163 (Fig. 2e)