In the present study, GCH1 overexpression restored decreased RyR2-mediated Ca2+ release by diabetes, and the beneficial effects of GCH-1 overexpression on RyR2-mediated Ca2+ release were abrogated by S-methyl-L-thiocitrulline (SMTC, a specific inhibitor of nNOS) (Fig. S8). Here, NOS1 is linked to diabetes mellitus.