Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis
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...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/29330 |
| _version_ | 1811201277073293312 |
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| author | Haruko Nakano Itsunari Minami Daniel Braas Herman Pappoe Xiuju Wu Addelynn Sagadevan Laurent Vergnes Kai Fu Marco Morselli Christopher Dunham Xueqin Ding Adam Z Stieg James K Gimzewski Matteo Pellegrini Peter M Clark Karen Reue Aldons J Lusis Bernard Ribalet Siavash K Kurdistani Heather Christofk Norio Nakatsuji Atsushi Nakano |
| author_facet | Haruko Nakano Itsunari Minami Daniel Braas Herman Pappoe Xiuju Wu Addelynn Sagadevan Laurent Vergnes Kai Fu Marco Morselli Christopher Dunham Xueqin Ding Adam Z Stieg James K Gimzewski Matteo Pellegrini Peter M Clark Karen Reue Aldons J Lusis Bernard Ribalet Siavash K Kurdistani Heather Christofk Norio Nakatsuji Atsushi Nakano |
| author_sort | Haruko Nakano |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:19:23Z |
| format | Article |
| id | doaj.art-c9808df6756440af9e5145aa0bbabc25 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:19:23Z |
| publishDate | 2017-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c9808df6756440af9e5145aa0bbabc252022-12-22T03:52:11ZengeLife Sciences Publications LtdeLife2050-084X2017-12-01610.7554/eLife.29330Glucose inhibits cardiac muscle maturation through nucleotide biosynthesisHaruko Nakano0https://orcid.org/0000-0001-5807-9127Itsunari Minami1Daniel Braas2Herman Pappoe3Xiuju Wu4Addelynn Sagadevan5Laurent Vergnes6Kai Fu7Marco Morselli8Christopher Dunham9Xueqin Ding10Adam Z Stieg11https://orcid.org/0000-0001-7312-9364James K Gimzewski12Matteo Pellegrini13https://orcid.org/0000-0001-9355-9564Peter M Clark14Karen Reue15Aldons J Lusis16Bernard Ribalet17Siavash K Kurdistani18Heather Christofk19Norio Nakatsuji20Atsushi Nakano21https://orcid.org/0000-0001-5702-5039Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United StatesInstitute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, JapanDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United StatesDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United StatesDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United StatesDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, United StatesDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United StatesDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United StatesDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United StatesDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United StatesCalifornia NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States; WPI Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, Meguro, JapanDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States; WPI Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, Meguro, Japan; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, United StatesDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United StatesDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, United States; Crump Institute for Molecular Imaging, University of California, Los Angeles, Los Angeles, United StatesDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United StatesDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, United States; Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United StatesDepartment of Physiology, University of California, Los Angeles, Los Angeles, United StatesJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United StatesDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United StatesInstitute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan; Institute for Life and Frontier Medical Sciences, Kyoto University, Kyoto, JapanDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United StatesThe 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.https://elifesciences.org/articles/29330human pluripotent stem celldiabetescardiac |
| spellingShingle | Haruko Nakano Itsunari Minami Daniel Braas Herman Pappoe Xiuju Wu Addelynn Sagadevan Laurent Vergnes Kai Fu Marco Morselli Christopher Dunham Xueqin Ding Adam Z Stieg James K Gimzewski Matteo Pellegrini Peter M Clark Karen Reue Aldons J Lusis Bernard Ribalet Siavash K Kurdistani Heather Christofk Norio Nakatsuji Atsushi Nakano Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis eLife human pluripotent stem cell diabetes cardiac |
| title | Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis |
| title_full | Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis |
| title_fullStr | Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis |
| title_full_unstemmed | Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis |
| title_short | Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis |
| title_sort | glucose inhibits cardiac muscle maturation through nucleotide biosynthesis |
| topic | human pluripotent stem cell diabetes cardiac |
| url | https://elifesciences.org/articles/29330 |
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