Glucagon contributes to liver zonation
Open accessAbstract
Significance: The lobules are the functional units of the liver. They consist of 15–25 layers of hepatocytes with specialized metabolic functions and gene expression patterns relative to their position along the lobule, a phenomenon referred to as metabolic zonation. The Wnt/β-catenin pathway regulates hepatocyte function but how the zonation is controlled to meet the metabolic demands of the liver is unclear. Glucagon regulates hepatic function. We now demonstrate that glucagon contributes to liver zonation by interacting and opposing the actions of the Wnt/β-catenin pathway.
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Higher periportal availability of hormones, such as insulin and glucagon, play important opposing roles in spatial metabolic zonation and interact with the WNT/β-catenin pathway.
“Higher periportal availability of hormones, such as insulin and glucagon, play important opposing roles in spatial metabolic zonation and interact with the WNT/β-catenin pathway.54”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [54]
The Discussion (page not available in our copy) says glucagon acts more strongly in the periportal zone and counteracts WNT/β-catenin signaling in liver metabolic zonation. The Results call insulin a counterregulatory hormone of glucagon, but the paper does not establish higher periportal insulin availability or an insulin interaction with WNT/β-catenin. (LLM, conf=0.87)
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Cites
Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling
de Lau, W., Barker, N., Low, T. Y., Koo, B., Li, V. S. W., Teunissen, H., Kujala, P., Haegebarth, A., Peters, P. J., van de Wetering, M., et al. (2011) · Nature · doi:10.1038/nature10337 · Cited by 1,267 · see citing works
Single-cell spatial reconstruction reveals global division of labour in the mammalian liver
Halpern, K. B., Shenhav, R., Matcovitch-Natan, O., Tóth, B., Lemze, D., Golan, M., Massasa, E. E., Baydatch, S., Landen, S., Moor, A. E., et al. (2017) · Nature · doi:10.1038/nature21065 · Cited by 1,059 · see citing works
Carmon, K. S., Gong, X. W., Lin, Q., Thomas, A., & Liu, Q. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106083108 · Cited by 857 · see citing works
Functional specialization of different hepatocyte populations
Jungermann, K. A., & Katz, N. R. (1989) · Physiological Reviews · doi:10.1152/physrev.1989.69.3.708 · Cited by 655 · see citing works
Zonation of parenchymal and nonparenchymal metabolism in liver.
Jungermann, K., & Keitzmann, T. (1996) · Annual Review of Nutrition · doi:10.1146/annurev.nu.16.070196.001143 · Cited by 589 · see citing works
High-throughput engineering of the mouse genome coupled with high-resolution expression analysis
Valenzuela, D. M., Murphy, A. J., Frendewey, D. A., Gale, N. W., Economides, A. N., Auerbach, W., Poueymirou, W. T., Adams, N. C., Rojas, J., Yasenchak, J., et al. (2003) · Nature Biotechnology · doi:10.1038/nbt822 · Cited by 585 · see citing works
Self-citationα-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains
Gromada, J., Franklin, I., & Wollheim, C. B. (2007) · Endocrine Reviews · doi:10.1210/er.2006-0007 · Cited by 574 · see citing works
Self-citationNitrogen metabolism and ornithine cycle function
Meijer, A. J., Lamers, W. H., & Chamuleau, R. A. F. M. (1990) · Physiological Reviews · doi:10.1152/physrev.1990.70.3.701 · Cited by 570 · see citing works
LGR4 and LGR5 are R‐spondin receptors mediating Wnt/β‐catenin and Wnt/PCP signalling
Glinka, A., Dolde, C. E., Kirsch, N., Huang, Y., Kazanskaya, O., Ingelfinger, D., Boutros, M., Cruciat, C., & Niehrs, C. (2011) · EMBO Reports · doi:10.1038/embor.2011.175 · Cited by 565 · see citing works
Gelling, R. W., Du, X. Q., Dichmann, D. S., Rømer, J., Huang, H., Cui, L., Obici, S., Tang, B., Holst, J. J., Fledelius, C., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0237106100 · Cited by 563 · see citing works
Apc Tumor Suppressor Gene Is the “Zonation-Keeper” of Mouse Liver
Benhamouche, S., Decaens, T., Godard, C., Chambrey, R., Rickman, D. S., Moinard, C., Vasseur-Cognet, M., Kuo, C. J., Kahn, A., Perret, C., et al. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.03.015 · Cited by 543 · see citing works
The RSPO–LGR4/5–ZNRF3/RNF43 module controls liver zonation and size
Planas-Paz, L., Orsini, V., Boulter, L., Calabrese, D., Pikiolek, M., Nigsch, F., Xie, Y., Roma, G., Donovan, A., Marti, P., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3337 · Cited by 359 · see citing works
Sekine, S., Lan, B. Y., Bedolli, M., Feng, S., & Hebrok, M. (2006) · Hepatology · doi:10.1002/hep.21131 · Cited by 295 · see citing works
Liver zonation: Novel aspects of its regulation and its impact on homeostasis
Gebhardt, R. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i26.8491 · Cited by 275 · see citing works
Beta-catenin signaling in murine liver zonation and regeneration: A Wnt-Wnt situation!
Yang, J., Mowry, L. E., Nejak‐Bowen, K. N., Okabe, H., Diegel, C. R., Lang, R. A., Williams, B. O., & Monga, S. P. (2014) · Hepatology · doi:10.1002/hep.27082 · Cited by 244 · see citing works
Differential gene expression in periportal and perivenous mouse hepatocytes
Braeuning, A., Ittrich, C., Köhle, C., Hailfinger, S., Bonin, M., Buchmann, A., & Schwarz, M. (2006) · The FEBS Journal · doi:10.1111/j.1742-4658.2006.05503.x · Cited by 240 · see citing works
Conarello, S. L., Jiang, G., Mu, J., Li, Z., Woods, J., Zycband, E., Ronan, J., Liu, F., Roy, R. S., Zhu, L., et al. (2006) · Diabetologia · doi:10.1007/s00125-006-0481-3 · Cited by 224 · see citing works
Dean, E. D., Li, M., Prasad, N., Wisniewski, S., Deylen, A. V., Spaeth, J. M., Maddison, L. A., Botros, A., Sedgeman, L. R., Bozadjieva-Kramer, N., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.011 · Cited by 207 · see citing works
The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation
Rocha, A. S., Vidal, V., Mertz, M., Kendall, T. J., Charlet, A., Okamoto, H., & Schedl, A. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.049 · Cited by 194 · see citing works
Self-citationT-cell factor 4 and β-catenin chromatin occupancies pattern zonal liver metabolism in mice
Gougelet, A., Torre, C., Veber, P., Sartor, C., Bachelot, L., Denechaud, P.-D., Godard, C., Moldes, M., Burnol, A.-F., Dubuquoy, C., et al. (2014) · Hepatology · doi:10.1002/hep.26924 · Cited by 190 · see citing works
Glucagon Couples Hepatic Amino Acid Catabolism to mTOR-Dependent Regulation of α-Cell Mass
Solloway, M. J., Madjidi, A., Gu, C., Eastham-Anderson, J., Clarke, H. J., Kljavin, N. M., Zavala‐Solorio, J., Kates, L., Friedman, B. A., Brauer, M., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.034 · Cited by 186 · see citing works
Kim, J., Okamoto, H., Huang, Z., Guillermo Anguiano, L., Chen, S., Liu, Q., Cavino, K., Xin, Y., Na, E., Hamid, R., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.006 · Cited by 183 · see citing works
Self-citationLiver Zonation Occurs Through a β-Catenin–Dependent, c-Myc–Independent Mechanism
Burke, Z. D., Reed, K. R., Phesse, T. J., Sansom, O. J., Clarke, A. R., & Tosh, D. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.02.063 · Cited by 163 · see citing works
Glycemic Control in Mice with Targeted Disruption of the Glucagon Receptor Gene
Parker, J. C., Andrews, K. M., Allen, M. R., Stock, J. L., & McNeish, J. D. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.6265 · Cited by 160 · see citing works
Endothelial Wnt/β-catenin signaling reduces immune cell infiltration in multiple sclerosis
Lengfeld, J. E., Lutz, S. E., Smith, J. R., Diaconu, C., Scott, C., Kofman, S. B., Choi, C., Walsh, C. M., Raine, C. S., Agalliu, I., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1609905114 · Cited by 152 · see citing works
Gebhardt, R., & Hovhannisyan, A. (2009) · Developmental Dynamics · doi:10.1002/dvdy.22041 · Cited by 101 · see citing works
Okamoto, H., Kim, J., Aglione, J., Lee, J., Cavino, K., Na, E., Rafique, A., Kim, J. H., Harp, J., Valenzuela, D. M., et al. (2015) · Endocrinology · doi:10.1210/en.2015-1011 · Cited by 100 · see citing works
Self-citationRole and Regulation of β-Catenin Signaling During Physiological Liver Growth
Monga, S. P. (2014) · Gene Expression · doi:10.3727/105221614x13919976902138 · Cited by 99 · see citing works
Wnt/β-catenin signaling in hepatic organogenesis
Nejak-Bowen, K., & Monga, S. P. S. (2008) · Organogenesis · doi:10.4161/org.4.2.5855 · Cited by 92 · see citing works
Webb, G. C., Akbar, M. S., Zhao, C., Swift, H. H., & Steiner, D. F. (2002) · Diabetes · doi:10.2337/diabetes.51.2.398 · Cited by 88 · see citing works
Compartmental modeling of glucagon kinetics in the conscious dog
Dobbins, R. L., Davis, S. N., Neal, D. W., Cobelli, C., Jaspan, J., & Cherrington, A. D. (1995) · Metabolism · doi:10.1016/0026-0495(95)90051-9 · Cited by 72 · see citing works
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Ben-Moshe, S., & Itzkovitz, S. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0134-x · Cited by 485 · see citing works
Glucagon Receptor Signaling and Glucagon Resistance
Janah, L., Kjeldsen, S. A. S., Galsgaard, K. D., Winther‐Sørensen, M., Stojanovska, E., Pedersen, J., Knop, F. K., Holst, J. J., & Albrechtsen, N. J. W. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133314 · Cited by 205 · see citing works
Hildebrandt, F., Andersson, A., Saarenpää, S., Larsson, L., Hul, N. V., Kanatani, S., Masek, J., Ellis, E. C. S., Barragán, A., Mollbrink, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27354-w · Cited by 195 · see citing works
Liver Zonation – Revisiting Old Questions With New Technologies
Cunningham, R. P., & Porat‐Shliom, N. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.732929 · Cited by 166 · see citing works
The Liver–α-Cell Axis and Type 2 Diabetes
Albrechtsen, N. J. W., Pedersen, J., Galsgaard, K. D., Winther‐Sørensen, M., Suppli, M. P., Janah, L., Gromada, J., Vilstrup, H., Knop, F. K., & Holst, J. J. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00251 · Cited by 149 · see citing works
Self-citationZimmermann, T., Thomas, L., Baader-Pagler, T., Haebel, P., Simon, E., Reindl, W., Bajrami, B., Rist, W., Uphues, I., Drucker, D. J., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101633 · Cited by 149 · see citing works
The Source of Glycolytic Intermediates in Mammalian Tissues
TeSlaa, T. A., Bartman, C., Jankowski, C. S. R., Zhang, Z., Xu, X., Xing, X., Wang, L., Lu, W., Hui, S. T., & Rabinowitz, J. D. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2020.12.020 · Cited by 120 · see citing works
Spatiotemporal Metabolic Liver Zonation and Consequences on Pathophysiology
Martini, T., Naef, F., & Tchorz, J. S. (2023) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-031521-024831 · Cited by 113 · see citing works
Ang, C. H., Hsu, S. H., Guo, F., Tan, C. T., Yu, V. C., Visvader, J. E., Chow, P. K. H., & Fu, N. Y. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908099116 · Cited by 102 · see citing works
Spatial metabolomics and its application in the liver
Santos, A. A., Delgado, T. C., Marques, V., Ramírez-Moncayo, C., Alonso, C., Vidal‐Puig, A., Hall, Z., Martínez‐Chantar, M. L., & Rodrigues, C. M. P. (2023) · Hepatology · doi:10.1097/hep.0000000000000341 · Cited by 100 · see citing works
Kietzmann, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092347 · Cited by 90 · see citing works
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Eriksen, P. L., Vilstrup, H., Rigbolt, K., Suppli, M. P., Sørensen, M., Heebøll, S., Veidal, S. S., Knop, F. K., & Thomsen, K. L. (2019) · Liver International · doi:10.1111/liv.14205 · Cited by 81 · see citing works
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Zhou, Y., Eid, T., Hassel, B., & Danbolt, N. C. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104809 · Cited by 76 · see citing works
Galsgaard, K. D., Jepsen, S. L., Kjeldsen, S. A. S., Pedersen, J., Albrechtsen, N. J. W., & Holst, J. J. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00459.2019 · Cited by 63 · see citing works
Jung, Y., Stratton, S. A., Lee, S. H., Kim, M. J., Jun, S., Zhang, J., Zheng, B., Cervantes, C., Cha, J., Barton, M. C., et al. (2020) · Hepatology · doi:10.1002/hep.31305 · Cited by 61 · see citing works
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Goldfarb, C. N., Karri, K., Pyatkov, M., & Waxman, D. J. (2022) · Endocrinology · doi:10.1210/endocr/bqac059 · Cited by 46 · see citing works
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Berndt, N., Kolbe, E., Gajowski, R., Eckstein, J., Ott, F., Meierhofer, D., Holzhütter, H., & Matz‐Soja, M. (2020) · Hepatology · doi:10.1002/hep.31274 · Cited by 54 · see citing works
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de Haan, W., Dheedene, W., Apelt, K., Décombas-Deschamps, S., Vinckier, S., Verhulst, S., Conidi, A., Deffieux, T., Staring, M. W., Vandervoort, P., et al. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab148 · Cited by 53 · see citing works
Wang, M.-Y., Zhang, Z., Zhao, S., Onodera, T., Sun, X.-N., Zhu, Q., Li, C., Li, N., Chen, S., Paredes, M., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.024 · Cited by 52 · see citing works
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Panday, R., Monckton, C. P., & Khetani, S. R. (2022) · Seminars in Liver Disease · doi:10.1055/s-0041-1742279 · Cited by 44 · see citing works
Scheidecker, B., Shinohara, M., Sugimoto, M., Danoy, M., Nishikawa, M., & Sakai, Y. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00524 · Cited by 36 · see citing works
Egnatchik, R. A., Leamy, A. K., Sacco, S. A., Cheah, Y. E., Shiota, M., & Young, J. D. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004869 · Cited by 35 · see citing works
The contributions of mesoderm-derived cells in liver development
Li, Y., Li, L., Lamaoqiezhong, Wang, X., Wang, W., Wang, Y., & Xu, C. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.09.003 · Cited by 35 · see citing works
Graphene Oxide Causes Disordered Zonation Due to Differential Intralobular Localization in the Liver
Wu, Y., Feng, W., Liu, R., Xia, T., & Liu, S. (2019) · ACS Nano · doi:10.1021/acsnano.9b08127 · Cited by 33 · see citing works
Art of Making Artificial Liver: Depicting Human Liver Biology and Diseases in Mice
Sugahara, G., Ishida, Y., Sun, J. C., Tateno, C., & Saito, T. (2020) · Seminars in Liver Disease · doi:10.1055/s-0040-1701444 · Cited by 31 · see citing works
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In vivo studies of glucagon secretion by human islets transplanted in mice
Tellez, K., Hang, Y., Gu, X.-Y., Chang, C. A., Stein, R., & Kim, S. K. (2019) · Nature Metabolism · doi:10.1038/s42255-020-0213-x · Cited by 23 · see citing works
Self-citationGillen, A. E., Fu, R., Riemondy, K. A., Jager, J., Fang, B., Lazar, M. A., & Martin, S. L. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.662132 · Cited by 28 · see citing works
Rodríguez, J. M. M., Frisk, A.-L., Kreutzer, R., Lemarchand, T., Lezmi, S., Saravanan, C., Stierstorfer, B., Thuilliez, C., Vezzali, E., Wieczorek, G., et al. (2023) · Toxicologic Pathology · doi:10.1177/01926233231178282 · Cited by 26 · see citing works
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Mak, K. M., & Png, C. Y. M. (2019) · The Anatomical Record · doi:10.1002/ar.24273 · Cited by 25 · see citing works
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Zhou, Y., Zhao, Y., Carbonaro, M., Chen, H., Germino, M., Adler, C., Ni, M., Zhu, Y. O., Kim, S. Y., Altarejos, J., et al. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155830 · Cited by 24 · see citing works
Self-citationMolecular regulation of mammalian hepatic architecture
Huppert, S. S., & Iwafuchi, M. (2018) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2018.12.003 · Cited by 23 · see citing works
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Campbell, S. A., Stephan, T. L., Lotto, J., Cullum, R., Drissler, S., & Hoodless, P. A. (2021) · Development · doi:10.1242/dev.199814 · Cited by 22 · see citing works
Hepatocyte size fractionation allows dissection of human liver zonation
Ölander, M., Wegler, C., Flörkemeier, I., Treyer, A., Handin, N., Pedersen, J. M., Vildhede, A. M., Mateus, A., LeCluyse, E. L., Urdzik, J., et al. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30273 · Cited by 21 · see citing works
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Jiang, Z., White, R. A., & Wang, T. C. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.04.003 · Cited by 20 · see citing works
Zhu, D., Rostami, M. R., Zuo, W.-L., Leopold, P. L., & Crystal, R. G. (2020) · Human Gene Therapy · doi:10.1089/hum.2019.366 · Cited by 18 · see citing works
Okada, J., Landgraf, A., Xiaoli, A. M., Liu, L. P., Horton, M., Schuster, V. L., Yang, F., Sidoli, S., Qiu, Y., Kurland, I. J., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01269-y · Cited by 16 · see citing works
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Rose, A. J. (2019) · Nutrients · doi:10.3390/nu11091990 · Cited by 15 · see citing works
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Self-citationKjeldsen, S. A. S., Werge, M. P., Grandt, J., Richter, M. M., Thing, M., Hetland, L. E., Rashu, E. B., Jensen, A. H., Winther‐Sørensen, M., Kellemann, J. S., et al. (2024) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00147.2024 · Cited by 6 · see citing works
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Long, J. J., Nijhar, K., Jenkins, R. T., Yassine, A., Motter, J. D., Jackson, K. R., Jerman, S., Besharati, S., Anders, R. A., Dunn, T. B., et al. (2023) · Liver Transplantation · doi:10.1097/lvt.0000000000000064 · Cited by 6 · see citing works
Scheidecker, B., Poulain, S., Sugimoto, M., Kido, T., Kawanishi, T., Miyajima, A., Kim, S. H., Arakawa, H., Kato, Y., Nishikawa, M., et al. (2024) · Biofabrication · doi:10.1088/1758-5090/ad30c5 · Cited by 5 · see citing works
Self-citationKasahara, D., Sumiyoshi, H., Endo, H., Yanagawa, T., Nakano, Y., Matsuki, Y., Nakao, S., Kamiya, A., Kimura, H., & Inagaki, Y. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.05.202 · Cited by 5 · see citing works
Towards a reference cell atlas of liver diversity over the human lifespan
Taylor, S. A., Bader, G. D., MacParland, S. A., Mullen, A. C., Andrews, T. S., Cuenca, A. G., DasGupta, R., Gehring, A. J., Grün, D., Guilliams, M., et al. (2025) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01114-3 · Cited by 4 · see citing works
Recapitulating the liver niche in vitro
Yap, K. K., & Mitchell, G. M. (2022) · Advances in stem cells and their niches · doi:10.1016/bs.asn.2021.10.002 · Cited by 3 · see citing works
Kjærgaard, K., Eriksen, P. L., Nøhr, T. K., Pedersen, S. B., Gravholt, C. H., Vilstrup, H., & Thomsen, K. L. (2024) · Metabolic Brain Disease · doi:10.1007/s11011-024-01434-4 · Cited by 4 · see citing works
Lu, S., Liu, G., Chen, T., Wang, W., Hu, J., Tang, D., & Peng, X. (2020) · Human Gene Therapy · doi:10.1089/hum.2019.322 · Cited by 3 · see citing works
Structure, Function and Responses to Injury
Crawford, J. M., Bioulac‐Sage, P., & Hytiroglou, P. (2023) · Elsevier eBooks · doi:10.1016/b978-0-7020-8228-3.00001-6 · Cited by 3 · see citing works
Scheidecker, B., Poulain, S., Sugimoto, M., Arakawa, H., Kim, S. H., Kawanishi, T., Kato, Y., Danoy, M., Nishikawa, M., & Sakai, Y. (2024) · Biotechnology and Bioengineering · doi:10.1002/bit.28653 · Cited by 3 · see citing works
Self-citationGalsgaard, K. D., Jepsen, S. L., Kjeldsen, S. A. S., Pedersen, J., Albrechtsen, N. J. W., & Holst, J. J. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/792119 · Cited by 3 · see citing works
Epigenetic regulation in MASLD – insight for therapeutic target discovery
Britsemmer, J. H., López‐Alcántara, N., & Kirchner, H. (2026) · Epigenomics · doi:10.1080/17501911.2026.2633978 · Cited by 2 · see citing works
In vivo visualization of bioactive iron and oxygen using LiON, the labile iron and oxygen notifier
Maeda, A., Nita, A., Sashiyama, S., Yoshitomo, S., Jepkosgei, K., Xu, Y., Arima, Y., Nakayama, K. I., Araki, K., & Moroishi, T. (2026) · Cell Reports Methods · doi:10.1016/j.crmeth.2026.101431 · Cited by 2 · see citing works
Hepatic Glucagon Signaling Regulates PCSK9 and Low-Density Lipoprotein Cholesterol
Spolitu, S., Okamoto, H., Dai, W., Zadroga, J. A., Wittchen, E. S., Gromada, J., & Özcan, L. (2019) · Circulation Research · doi:10.1161/circresaha.118.313648 · Cited by 62 · see citing works
Self-citationEstes, S. K., Shiota, C., O’Brien, T. P., Printz, R. L., & Shiota, M. (2024) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00192.2023 · Cited by 1 · see citing works
GCGR: novel potential therapeutic target for chronic kidney disease
Hu, Y., Huang, H., & Xiang, R. (2024) · Science China Life Sciences · doi:10.1007/s11427-024-2576-x · Cited by 1 · see citing works
Murad, W., Abbass, T., & Seddek, A. (2018) · Archives of Toxicology · doi:10.1007/s00204-018-2310-0 · Cited by 1 · see citing works
Trefts, E. (2019) · Cited by 1 · see citing works
A spatial atlas of Wnt and Frizzled receptor expression in adult mouse liverPreprint
Gayden, J. D., Hu, S., Joseph, P., Delgado, E. R., Liu, S., Bell, A. W., Puig, S., Monga, S. P., & Freyberg, Z. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.23.509269
hESCs-derived organoids achieve liver zonation by LSEC modulationPreprint
Zhang, Y., Huang, C., Sun, L., Zhou, L., Liang, K., Niu, Y., Wu, B., & Du, Y. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.05.592562
In vivo visualization of bioactive iron and oxygen using the Labile Iron and Oxygen Notifier (LiON)Preprint
Moroishi, T., Maeda, A., Nita, A., Sashiyama, S., Jepkosgei, K., Xu, Y., Arima, Y., Nakayama, K. I., Araki, K., & Yoshitomo, S. (2025) · Research Square · doi:10.21203/rs.3.rs-6892412/v1
Shao, C., Yang, X., Jing, Y., Hou, X., Huang, Y., Zong, C., Gao, L., Liu, W., Jiang, J., Ye, F., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14767018
Shao, C., Yang, X., Jing, Y., Hou, X., Huang, Y., Zong, C., Gao, L., Liu, W., Jiang, J., Ye, F., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14767021
Shao, C., Yang, X., Jing, Y., Hou, X., Huang, Y., Zong, C., Gao, L., Liu, W., Jiang, J., Ye, F., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14767009
Shao, C., Yang, X., Jing, Y., Hou, X., Huang, Y., Zong, C., Gao, L., Liu, W., Jiang, J., Ye, F., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14767027
Shao, C., Yang, X., Jing, Y., Hou, X., Huang, Y., Zong, C., Gao, L., Liu, W., Jiang, J., Ye, F., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14767012
Shao, C., Yang, X., Jing, Y., Hou, X., Huang, Y., Zong, C., Gao, L., Liu, W., Jiang, J., Ye, F., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14767024
Shao, C., Yang, X., Jing, Y., Hou, X., Huang, Y., Zong, C., Gao, L., Liu, W., Jiang, J., Ye, F., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14767015
Shiojiri, N., Ota, N., Hirose, H., Fukuda, T., Kato, H., Maeda, H., Takabayashi, S., Kawasaki, T., & Ikeo, K. (2026) · Cell and Tissue Research · doi:10.1007/s00441-026-04063-8
Influence du sexe dans la susceptibilité aux hépatopathies métaboliques
Smati, S. (2019) · theses.fr (ABES) · doi:10.70675/01997f55za990z41e6z96baz8221de2a6281
Aizenshtadt, A., Dalmao‐Fernández, A., Stokowiec, J., Kømurcu, K. S., Ali, T. M. L., Erlandsson, T. M., Skottvoll, F. S., Busek, M., Golovin, A., Øynebråten, I., et al. (2026) · Advanced Healthcare Materials · doi:10.1002/adhm.71834
- Authors
- Cheng, X., Kim, S. Y., Okamoto, H., Xin, Y., Yancopoulos, G. D., Murphy, A. J., & Gromada, J.
- Affiliations
- Regeneron (United States) (US)
- Corresponding author
- Yancopoulos, George D.
- Gromada, Jesper
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2018-03-19
- Volume
- 115
- Issue
- 17
- Pages
- E4111-E4119
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5924920
- OpenAlex
- W2792330843
- Cited by
- 90
- References
- 31
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 11 · 2023: 8 · 2022: 8 · 2021: 17 · 2020: 12 · 2019: 16 · 2018: 8
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- glucagon, liver zonation, Wnt/β-catenin signaling, periportal hepatocytes, perivenous hepatocytes, hepatic lobule, gene expression regulation, metabolic zonation, glucagon receptor
- MeSH terms
- Animals, Gene Expression Regulation, Glucagon, Liver, Mice, Knockout, Hepatocytes, Mice, Wnt Signaling Pathway
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