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Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis
Open accessAbstract
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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“Using a model of STZ-induced insulin-deficient diabetes during pregnancy, Nakano et al. demonstrated that hyperglycemia promotes the proliferation of fetal offspring cardiomyocytes while maturation was inhibited [117].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [117]
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“Using a model of STZ-induced insulin-deficient diabetes during pregnancy, Nakano et al. demonstrated that hyperglycemia promotes the proliferation of fetal offspring cardiomyocytes while maturation was inhibited [117].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [117]
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
A gene atlas of the mouse and human protein-encoding transcriptomes
Su, A. I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K. A., Block, D., Zhang, J., Soden, R., Hayakawa, M., Kreiman, G., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400782101 · Cited by 3,475
Targeting cancer metabolism: a therapeutic window opens
Heiden, M. G. V. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3504 · Cited by 1,443
Functional Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells
Zhang, J., Wilson, G. F., Soerens, A. G., Koonce, C. H., Yu, J., Palecek, S. P., Thomson, J. A., & Kamp, T. J. (2009) · Circulation Research · doi:10.1161/circresaha.108.192237 · Cited by 1,426
Targeting metabolic transformation for cancer therapy
Tennant, D. A., Durán, R. V., & Gottlieb, E. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2817 · Cited by 1,073
Tohyama, S., Hattori, F., Sano, M., Hishiki, T., Nagahata, Y., Matsuura, T., Hashimoto, H., Suzuki, T., Yamashita, H., Satoh, Y., et al. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.09.013 · Cited by 1,045
Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells
Carey, B. W., Finley, L. W. S., Cross, J. R., Allis, C. D., & Thompson, C. B. (2015) · Nature · doi:10.1038/nature13981 · Cited by 1,007
Ma, J., Guo, L., Fiene, S., Anson, B. D., Thomson, J. A., Kamp, T. J., Kolaja, K. L., Swanson, B. J., & January, C. T. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00694.2011 · Cited by 787
Congenital Heart Disease in Adults
Brickner, M. E., Hillis, L. D., & Lange, R. A. (2000) · New England Journal of Medicine · doi:10.1056/nejm200001273420407 · Cited by 765
Influence of Threonine Metabolism on S -Adenosylmethionine and Histone Methylation
Shyh-Chang, N., Locasale, J. W., Lyssiotis, C. A., Zheng, Y., Teo, R. Y., Ratanasirintrawoot, S., Zhang, J., Onder, T., Unternaehrer, J. J., Zhu, H., et al. (2013) · Science · doi:10.1126/science.1226603 · Cited by 638
Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage
Wamstad, J. A., Alexander, J. M., Truty, R., Shrikumar, A., Li, F., Eilertson, K. E., Ding, H., Wylie, J. N., Pico, A. R., Capra, J. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.07.035 · Cited by 624
Ruijtenberg, S., & van den Heuvel, S. (2016) · Cell Cycle · doi:10.1080/15384101.2015.1120925 · Cited by 577
Wang, J., Takeuchi, T., Tanaka, S., Kubo, S.-K., Kayo, T., Lu, D., Takata, K., Koizumi, A., & Izumi, T. (1999) · Journal of Clinical Investigation · doi:10.1172/jci4431 · Cited by 572
Genetics of Congenital Heart Disease
Fahed, A. C., Gelb, B. D., Seidman, J. G., & Seidman, C. E. (2013) · Circulation Research · doi:10.1161/circresaha.112.300853 · Cited by 564
Yoshioka, M., Kayo, T., Ikeda, T., & Koizuni, A. (1997) · Diabetes · doi:10.2337/diab.46.5.887 · Cited by 536
Methionine Metabolism Regulates Maintenance and Differentiation of Human Pluripotent Stem Cells
Shiraki, N., Shiraki, Y., Tsuyama, T., Obata, F., Miura, M., Nagae, G., Aburatani, H., Kume, K., Endo, F., & Kume, S. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.017 · Cited by 524
Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor
Krall, A. S., Xu, S., Graeber, T. G., Braas, D., & Christofk, H. R. (2016) · Nature Communications · doi:10.1038/ncomms11457 · Cited by 504
Self-citationGENETICS of congenital heart disease.
(1955) · PubMed · Cited by 501
Generation of Induced Pluripotent Stem Cells from Human Cord Blood
Haase, A., Olmer, R., Schwanke, K., Wunderlich, S., Merkert, S., Hess, C. W., Zweigerdt, R., Gruh, I., Meyer, J., Wagner, S., et al. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.08.021 · Cited by 494
An expression atlas of human primary cells: inference of gene function from coexpression networks
Mabbott, N. A., Baillie, J. K., Brown, H. K., Freeman, T. C., & Hume, D. A. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-632 · Cited by 494
The Ins2 Akita Mouse as a Model of Early Retinal Complications in Diabetes
Barber, A. J., Antonetti, D. A., Kern, T. S., Reiter, C. E. N., Soans, R. S., Krady, J. K., Levison, S. W., Gardner, T. W., & Bronson, S. K. (2005) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-1340 · Cited by 472
Yang, X., Rodriguez, M. L., Pabon, L., Fischer, K. A., Reinecke, H., Regnier, M., Sniadecki, N. J., Ruohola‐Baker, H., & Murry, C. E. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.04.005 · Cited by 444
Young, C. S., Hicks, M. R., Ermolova, N. V., Nakano, H., Jan, M., Younesi, S., Karumbayaram, S., Kumagai-Cresse, C., Wang, D. D., Zack, J. A., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.01.021 · Cited by 384
Self-citationDeoxyriboside Control and Synchronization of Mitosis
Xeros, N. (1962) · Nature · doi:10.1038/194682a0 · Cited by 382
Dependence of Mouse Embryonic Stem Cells on Threonine Catabolism
Wang, J., Alexander, P. B., Wu, L. C., Hammer, R. E., Cleaver, O. B., & McKnight, S. L. (2009) · Science · doi:10.1126/science.1173288 · Cited by 365
San Martín, A., Ceballo, S., Ruminot, I., Lerchundi, R., Frommer, W. B., & Barros, L. F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057712 · Cited by 361
Paige, S. L., Thomas, S., Stoick-Cooper, C. L., Wang, H., Maves, L., Sandstrom, R. S., Pabon, L., Reinecke, H., Pratt, G. A., Keller, G. M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.027 · Cited by 332
Huebsch, N., Loskill, P., Mandegar, M. A., Marks, N. C., Sheehan, A. S., Ma, Z., Mathur, A., Nguyen, T., Yoo, J. C., Judge, L. M., et al. (2014) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2014.0283 · Cited by 313
Glucose and Glutamine Metabolism Regulate Human Hematopoietic Stem Cell Lineage Specification
Oburoglu, L., Tardito, S., Fritz, V., de Barros, S. C., Mérida, P., Craveiro, M., Mamede, J. I., Cretenet, G., Mongellaz, C., An, X., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.06.002 · Cited by 312
Obesity, gestational diabetes and pregnancy outcome
Yogev, Y., & Visser, G. H. A. (2008) · Seminars in Fetal and Neonatal Medicine · doi:10.1016/j.siny.2008.09.002 · Cited by 284
Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells
Tohyama, S., Fujita, J., Hishiki, T., Matsuura, T., Hattori, F., Ohno, R., Kanazawa, H., Seki, T., Nakajima, K., Kishino, Y., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.03.001 · Cited by 263
Minami, I., Yamada, K., Otsuji, T. G., Yamamoto, T., Shen, Y., Otsuka, S., Kadota, S., Morone, N., Barve, M. P., Asai, Y., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.09.015 · Cited by 248
Self-citationDrawnel, F. M., Boccardo, S., Prummer, M., Delobel, F., Graff, A., Weber, M., Gérard, R., Badi, L., Kam-Thong, T., Bu, L., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.09.055 · Cited by 247
Birth defects in pregestational diabetes: Defect range, glycemic threshold and pathogenesis
Gabbay‐Benziv, R. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i3.481 · Cited by 177
The Congenital Heart Disease Genetic Network Study
Gelb, B. D., Brueckner, M., Chung, W. K., Goldmuntz, E., Kaltman, J. R., Kaski, J. P., Kim, R., Kline, J. K., Mercer-Rosa, L., Porter, G., et al. (2013) · Circulation Research · doi:10.1161/circresaha.111.300297 · Cited by 168
Diabetes and Congenital Heart Defects
Simeone, R. M., Devine, O. J., Marcinkevage, J. A., Gilboa, S. M., Razzaghi, H., Bardenheier, B. H., Sharma, A. J., & Honein, M. A. (2014) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2014.09.002 · Cited by 124
Crespo, F. L., Sobrado, V. R., Gómez, L., Cervera, A. M., & McCreath, K. J. (2010) · Stem Cells · doi:10.1002/stem.441 · Cited by 123
Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo
Harris, J. M., Esain, V., Frechette, G. M., Harris, L. J., Cox, A. G., Cortes, M., Garnaas, M., Carroll, K. J., Cutting, C. C., Khan, T. M., et al. (2013) · Blood · doi:10.1182/blood-2012-12-471201 · Cited by 116
Maturation of fatty acid and carbohydrate metabolism in the newborn heart
Makinde, A.-O., Kantor, P. F., & Lopaschuk, G. D. (1998) · Molecular and Cellular Biochemistry · doi:10.1023/a:1006860104840 · Cited by 114
Multifactorial basis of the syndrome of diabetic embryopathy
Reece, E. A., Homko, C. J., & Wu, Y.-K. (1996) · Teratology · doi:10.1002/(sici)1096-9926(199610)54:4 · Cited by 105
Studies of mitochondrial development during embryogenesis in the rat
Mackler, B. F., Grace, R., & Duncan, H. M. (1971) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(71)90367-5 · Cited by 97
Unique Metabolic Features of Stem Cells, Cardiomyocytes, and Their Progenitors
Gaspar, J. A., Doss, M. X., Hengstler, J. G., Cadenas, C., Hescheler, J., & Sachinidis, A. (2014) · Circulation Research · doi:10.1161/circresaha.113.302021 · Cited by 92
Mitochondrial Ca2+ uptake by the voltage-dependent anion channel 2 regulates cardiac rhythmicity
Shimizu, H., Schredelseker, J., Huang, J., Lu, K., Naghdi, S., Lu, F., Franklin, S., Fiji, H. D. G., Wang, K., Zhu, H., et al. (2015) · eLife · doi:10.7554/elife.04801 · Cited by 88
Self-citationCELLULAR ENERGY METABOLISM DURING FETAL DEVELOPMENT
Warshaw, J. B., & Terry, M. L. (1970) · The Journal of Cell Biology · doi:10.1083/jcb.44.2.354 · Cited by 83
Rigid microenvironments promote cardiac differentiation of mouse and human embryonic stem cells
Arshi, A., Nakashima, Y., Nakano, H., Eaimkhong, S., Evseenko, D. A., Reed, J. C., Stieg, A. Z., Gimzewski, J. K., & Nakano, A. (2013) · Science and Technology of Advanced Materials · doi:10.1088/1468-6996/14/2/025003 · Cited by 75
Self-citationRegulatory mechanisms in the synthesis of deoxyribonucleic acid in vitro
Reichard, P. A., Canellakis, Z. N., & Canellakis, E. S. (1960) · Biochimica et Biophysica Acta · doi:10.1016/0006-3002(60)90067-6 · Cited by 58
John, S., Ottolia, M., Weiss, J. N., & Ribalet, B. (2007) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-007-0395-z · Cited by 48
Self-citationZhu, H., Scharnhorst, K. S., Stieg, A. Z., Gimzewski, J. K., Minami, I., Nakatsuji, N., Nakano, H., & Nakano, A. (2017) · Scientific Reports · doi:10.1038/srep43210 · Cited by 47
Self-citationMetabolite utilization by isolated embryonic rat hearts in vitro
Cox, S. J., & Gunberg, D. L. (1972) · Development · doi:10.1242/dev.28.2.235 · Cited by 40
Fujita, H., Haseyama, T., Kayo, T., Nozaki, J., Wada, Y., Ito, S., & Koizumi, A. (2001) · Nephron Experimental Nephrology · doi:10.1159/000052636 · Cited by 32
Yaguchi, M., Nagashima, K., Izumi, T., & Okamoto, K. (2003) · Neuropathology · doi:10.1046/j.1440-1789.2003.00475.x · Cited by 21
Linker, W., Löffler, M., & Schneider, F. (1985) · PubMed · Cited by 18
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Cardiomyocyte Maturation: New Phase in Development
Guo, Y., & Pu, W. T. (2020) · Circulation Research · doi:10.1161/circresaha.119.315862 · Cited by 653
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Feyen, D. A. M., McKeithan, W. L., Bruyneel, A. A. N., Spiering, S., Hörmann, L., Ulmer, B., Zhang, H., Briganti, F., Schweizer, M., Hegyi, B., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107925 · Cited by 400
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Metadata
- Authors
- Nakano, H., Minami, I., Braas, D., Pappoe, H., Wu, X., Sagadevan, A., Vergnes, L., Fu, K., Morselli, M., Dunham, C., Ding, X., Stieg, A. Z., Gimzewski, J. K., Pellegrini, M., Clark, P. M., Reue, K., Lusis, A. J., Ribalet, B., Kurdistani, S. K., Christofk, H., Nakatsuji, N., & Nakano, A.
- Affiliations
- University of California, Los Angeles (US)
- Kyoto University (JP)
- California NanoSystems Institute (US)
- Corresponding author
- Nakano, Haruko
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2017-12-12
- Volume
- 6
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5726851
- OpenAlex
- W2774527609
- Cited by
- 195
- References
- 54
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 26 · 2023: 28 · 2022: 37 · 2021: 36 · 2020: 16 · 2019: 15 · 2018: 7
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Oppenheimer Foundation
- University of California, Los Angeles (Center for Duchenne Muscular Dystrophy, Pilot and Feasibility Seed Grant program)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR057230)
- National Center for Research Resources (Grant S10RR026744)
- National Institutes of Health (DK094311, CA178415, HL126051, HL124503)
- Hunan University (Chinese Scholarship Council of Chemistry and Chemical Engineering)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- high glucose, cardiomyocyte maturation, nucleotide synthesis, pentose phosphate pathway, diabetes in pregnancy, maternal hyperglycemia, congenital heart disease, cardiomyopathy, pluripotent stem cell-derived cardiomyocytes, fetal heart development
- MeSH terms
- Animals, Cell Differentiation, Female, Glucose, Humans, Mice, Inbred C57BL, Myocardium, Nucleotides, Pentose Phosphate Pathway, Pregnancy, Sweetening Agents, Gene Expression Profiling, Muscle Development, Myocytes, Cardiac, Mice, Embryonic Stem Cells
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