Tale of two kinases: Protein kinase A and Ca2+/calmodulin-dependent protein kinase II in pre-diabetic cardiomyopathy

Metabolic syndrome is a pre-diabetic state characterized by several biochemical and physiological alterations, including insulin resistance, visceral fat accumulation, and dyslipidemias, which increase the risk for developing cardiovascular disease. Metabolic syndrome is associated with augmented sympathetic tone, which could account for the etiology of pre-diabetic cardiomyopathy. This review summarizes the current knowledge of the pathophysiological consequences of enhanced and sustained beta-adrenergic response in pre-diabetes, focusing on cardiac dysfunction reported in diet-induced experimental models of pre-diabetic cardiomyopathy. The research reviewed indicates that both protein kinase A and Ca2+/calmodulin-dependent protein kinase II play important roles in functional responses mediated by beta(1)-adrenoceptors; therefore, alterations in the expression or function of these kinases can be deleterious. This review also outlines recent information on the role of protein kinase A and Ca2+/calmodulin-dependent protein kinase II in abnormal Ca2+ handling by cardiomyocytes from diet-induced models of pre-diabetic cardiomyopathy.

Automated summary

Metabolic syndrome is a pre-diabetic state characterized by insulin resistance, visceral fat accumulation, and dyslipidemias, which increase the risk for developing cardiovascular disease. Increased synergistic tone in metabolic syndrome may contribute to the onset of pre-diabetic cardiomyopathy. The alterations in protein kinase A and Ca2+/calmodulin-dependent protein kinase II play important roles in functional responses mediated by beta(1)-adrenoceptors in pre-diabetes.