Journal article
Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis
eLife, v 6
12 Dec 2017
PMID: 29231167
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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Details
- Title
- Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis
- Creators
- Haruko Nakano - University of California, Los AngelesItsunari Minami - Kyoto UniversityDaniel Braas - University of California, Los AngelesHerman Pappoe - University of California, Los AngelesXiuju Wu - University of California, Los AngelesAddelynn Sagadevan - University of California, Los AngelesLaurent Vergnes - University of California, Los AngelesKai Fu - University of California, Los AngelesMarco Morselli - University of California, Los AngelesChristopher Dunham - University of California, Los AngelesXueqin Ding - University of California, Los AngelesAdam Z Stieg - California NanoSystems InstituteJames K Gimzewski - University of California, Los AngelesMatteo Pellegrini - California State University Los AngelesPeter M Clark - University of California, Los AngelesKaren Reue - California State University Los AngelesAldons J Lusis - University of California, Los AngelesBernard Ribalet - University of California, Los AngelesSiavash K Kurdistani - University of California, Los AngelesHeather Christofk - University of California, Los AngelesNorio Nakatsuji - Kyoto UniversityAtsushi Nakano - University of California, Los Angeles
- Publication Details
- eLife, v 6
- Publisher
- eLife
- Grant note
- S10 RR026744 / NCRR NIH HHS P30 AR057230 / NIAMS NIH HHS DP3 DK094311 / NIDDK NIH HHS P50 CA211015 / NCI NIH HHS R21 HL124503 / NHLBI NIH HHS R56 HL126051 / NHLBI NIH HHS P01 HL090553 / NHLBI NIH HHS R01 CA178415 / NCI NIH HHS P01 HL028481 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000417866600001
- Scopus ID
- 2-s2.0-85040929819
- Other Identifier
- 991019356342404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biology