Table 1

Cardiodepressant Effects of Metabolic Aberrations

AberrationEffect
Hyperglycemia⬆ Mitochondrial superoxide production,
⬇ nitric oxide and cGMP;
⬇ protein kinase G activity; hypophosphorylation of titin;
⬆ myocardial deposition of advanced glycation products due to nicotinamide adenine dinucleotide phosphate oxidase and inflammatory activation
⬆ FFA uptake into cardiomyocytesMitochondrial dysfunction with uncoupling of oxidative phosphorylation; cardiomyocyte lipoapoptosis
⬆ Myocardial triglyceride accumulationCardiomyocyte lipoapoptosis
⬆ Oxidative stress⬆ Nuclear factor kappa B;
⬆ cardioinhibitory and profibrotic cytokines; dysregulation of intracellular Ca+2 turnover (effect on Ca+2-sensitive contractile proteins, Na+/Ca+2 exchanger and sarcoplasmic or endoplasmic reticulum Ca+2–ATPase pump)
Insulin resistance and hyperinsulinemia⬆ Cardiomyocyte hypertrophy and intrinsic stiffness by the activation of phosphoinositide 3-kinase/protein kinase B cascade; activation of insulin-like growth factor 1 receptors, ⬆ response to angiotensin II; sodium retention with intravascular volume expansion

ATPase = adenosine triphosphatase; cGMP = cyclic guanosine monophosphate; FFA = free fatty acids.