AGE accumulation during diabetes, and to a less extent during aging, could contribute to the observed cardiomyopathy, since AGEs form irreversible cross-links with many proteins with low turnover rates, such as collagen but also intracellular cardiac SR proteins (i.e., SERCA2a pump and RyR2); however, their pathogenic role on excitation-contraction coupling has not been investigated. The gene discussed is RYR2; the disease is diabetes mellitus.