INS and overnutrition: In the heart, overnutrition concomitant with insulin resistance gives rise to enhanced stimulation of RAAS [90], which consequently supplements elevated activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and an increased production of cytosolic ROS, decreased bioavailable nitric oxide (NO), altered insulin signalling with respect to metabolism, and a dysfunctional diastolic phase [90, 91].