In diabetic cardiomyopathy, the mechanisms that regulate intracellular Ca2+ handling are altered and the function of RyR2 is clearly compromised; the latter has been associated with a decrease in RyR2 protein expression and reduced SR Ca2+ load (Pereira et al., 2014); however, the data concerning the contribution of RyRs to the Ca2+ mishandling in MetS cardiomyocytes has, until now, been lacking. This evidence concerns the gene RYR2 and diabetic cardiomyopathy.