Table 2

Effects of diabetes (hyperglycemia, hyperlipidemia, insulin resistance, insulin deficiency) on myocardial function (20)

Altered Ca2++ handling
 Decreased sarcoendoplastic reticulum Ca2++ –ATPase 2A
 Decreased expression of Ca2++ –ATPase 2A, Na2+/Ca2+ exchanger
 Decreased excitation-contraction coupling
Cardiac insulin resistance
 Increased mitochondrial reactive oxygen species formation
 Increased mitochondrial uncoupling
 Decreased mitochondrial function
 Decreased glucose oxidation and increased fatty acid oxidation
Increased lipid uptake
 Increased peroxisome proliferator–activated receptor α activation
 Decreased glucose oxidation and increased fatty acid oxidation
 Accumulation of ceramides
 Increased lipotoxicity
 Increased apoptosis
Glucotoxicity
 Increased mitochondrial reactive oxygen species formation
 Increased PKC activity
 Increased AGE formation
 Increased fibrosis
Increased renin-angiotensin-aldosterone system activation
 Increased fibrosis
 Increased apoptosis
 Increased hypertrophy