The results indicated that ovariectomized ERα/β DKO mice were more susceptible to STZ-induced islet apoptosis and diabetes as compared with sham-operated ERα/β DKO mice, but the STZ-induced islet apoptosis and diabetes in ovariectomized ERα/β DKO mice were attenuated by E2 replacement therapy (149), suggesting that E2/GPER signaling is protective against STZ-induced insulin deficient diabetes. Here, ESR1 is linked to diabetes mellitus.