High glucose inhibits the maturation of cardiomyocytes by promoting nucleotide biosynthesis through the pentose phosphate pathway, providing a possible mechanism for congenital heart disease.
Does high glucose exposure inhibit cardiac muscle maturation in developing cardiomyocytes?
High glucose suppresses cardiac maturation by promoting nucleotide biosynthesis, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy.
The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway. Blood glucose level in embryos is stable in utero during normal pregnancy, but glucose uptake by fetal cardiac tissue is drastically reduced in late gestational stages. In a murine model of diabetic pregnancy, fetal hearts showed cardiomyopathy with increased mitotic activity and decreased maturity. These data suggest that high glucose suppresses cardiac maturation, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy.
Nakano et al. (Mon,) conducted a other in Congenital heart disease in diabetic pregnancy. High glucose was evaluated on Cardiomyocyte maturation. High glucose inhibits the maturation of cardiomyocytes by promoting nucleotide biosynthesis through the pentose phosphate pathway, providing a possible mechanism for congenital heart disease.