The changes of fructos-2,6-bisphosphate level in transgenic mice causing cardiomyopathy.

Abstract

Heart failure is recognized as a major cause of death among diabetics. In type I and II diabetes, glucose uptake, glycolysis and pyruvate oxidation are impaired, and fatty acid utilization increases. These alterations in metabolism contribute toward cardiac contractile function. There is a gap in our understanding on how alterations in glycolytic metabolite fructose-2,6-bisphosphate (F-2,6-P 2 ) affects cardiac dysfunction. Two cardiac-specific overexpression of PFK-2 (phosphofructose kinase-2) transgenic models were used to investigate the role of altered metabolism by F-2,6-P 2 in provoking cardiomyopathy. One model is with the PFK-2 kinase active and phosphatase inactive enzyme called MK and another model is the PFK-2 kinase inactive and phosphatase active enzyme called Mb. The effect of PFK2 transgenes was evaluated by Langendorff-perfused heart in vitro. Cardiomyopathy was assessed by measurement of heart to body weight ratio and cardiac histology. The study shows that changes in F-2,6-P 2 level could induce cardiac hypertrophy and fibrosis and cause cardiac dysfunction, and may be important to development of diabetic cardiomyopathy