TY - JOUR TI - Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis AU - Nakano, Haruko AU - Minami, Itsunari AU - Braas, Daniel AU - Pappoe, Herman AU - Wu, Xiuju AU - Sagadevan, Addelynn AU - Vergnes, Laurent AU - Fu, Kai AU - Morselli, Marco AU - Dunham, Christopher AU - Ding, Xueqin AU - Stieg, Adam Z AU - Gimzewski, James K AU - Pellegrini, Matteo AU - Clark, Peter M AU - Reue, Karen AU - Lusis, Aldons J AU - Ribalet, Bernard AU - Kurdistani, Siavash K AU - Christofk, Heather AU - Nakatsuji, Norio AU - Nakano, Atsushi A2 - Yelon, Deborah VL - 6 PY - 2017 DA - 2017/12/12 SP - e29330 C1 - eLife 2017;6:e29330 DO - 10.7554/eLife.29330 UR - https://doi.org/10.7554/eLife.29330 AB - 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. KW - human pluripotent stem cell KW - diabetes KW - cardiac JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -