This increased MC5R expression probably being a defensive and anti-hypertrophic response to the high-glucose induced damage, since by activating MC5Rwith α-MSH or with PG-901 the cell viability was increased and the cardiac hypertrophy markers, including the high intracellular glucose content (detected by ATP levels determination), were decreased compared to cells exposed to high glucose only. Here, MC5R is linked to cardiac hypertrophy.