In addition to cardiac hypertrophy-related mitogen-activated protein kinases (MAPK) pathways (e.g., p38, c-Jun N-terminal kinases (JNK) and extracellularly responsive kinase (ERK1/2)), the IL-6/MEK5/ERK5 signaling pathway was greatly activated in the diabetic rat hearts, which contributes to the up-regulation of cardiac pathologic hypertrophy markers including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), and leads to cardiac contractile dysfunction. Here, NPPA is linked to cardiac hypertrophy.