Ca 2 + cell physiology in smooth muscle 221 4.1 Smooth muscle cell classification 221 4.2 Ca 2 + homeostasis 223 4.3 Ca 2 + release channels in ER 225 4.4 Ca 2 + refill mechanisms in ER 227 4.5 Excitation-contraction coupling 228 5. SR/ER dysfunction and diseases 230 5.1 SR dysfunction and cardiac hypertrophy 230 5.2 SR and insulin resistance in skeletal muscle cells 236 5.3 ER in smooth muscle cell and hypertension 240 6. Concluding remarks 241 Acknowledgments 243 References 243

Diabetic cardiomyopathy (DCM) is a severe complication of diabetes developed mainly in poorly controlled patients. In DCM, several clinical manifestations as well as cellular and molecular mechanisms contribute to its phenotype. The production of reactive oxygen species (ROS), chronic low-grade inflammation, mitochondrial dysfunction, autophagic flux inhibition, altered metabolism, dysfunctional insulin signaling, cardiomyocyte hypertrophy, cardiac fibrosis, and increased myocardial cell death are described as the cardinal features involved in the genesis and development of DCM. However, many of these features can be associated with broader cellular processes such as inflammatory signaling, mitochondrial alterations, and autophagic flux inhibition. In this review, these mechanisms are critically discussed, highlighting the latest evidence and their contribution to the pathogenesis of DCM and their potential as pharmacological targets.

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