This study is the first to report that the downregulation of Cx43 expression is associated with reduced ferroptosis and enhanced tolerance to MIRI in early-stage type 1 diabetic rodents while increased Cx43 and subsequent increase in ferroptosis at late-stage diabetes (i.e., 5-week diabetes in the current study) are attributable to increased myocardial susceptibility to MIRI in diabetes. Here, GJA1 is linked to type 1 diabetes mellitus.