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GLP-1R Agonists Promote Normal and Neoplastic Intestinal Growth through Mechanisms Requiring Fgf7
Open accessAbstract
Glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L cells promotes nutrient disposal via the incretin effect. However, the majority of L cells are localized to the distal gut, suggesting additional biological roles for GLP-1. Here, we demonstrate that GLP-1 receptor (GLP-1R) signaling controls mucosal expansion of the small bowel (SB) and colon. These actions did not require the epidermal growth factor (EGF) or intestinal epithelial insulin-like growth factor (IGF1) receptors but were absent in Glp1r(-/-) mice. Polyp number and size were increased in SB of exendin-4-treated Apc(Min/+) mice, whereas polyp number was reduced in SB and colon of Glp1r(-/-):Apc(Min/+) mice. Exendin-4 increased fibroblast growth factor 7 (Fgf7) expression in colonic polyps of Apc(Min/+) mice and failed to increase intestinal growth in mice lacking Fgf7. Exogenous exendin-4 and Fgf7 regulated an overlapping set of genes important for intestinal growth. Thus, gain and loss of GLP-1R signaling regulates gut growth and intestinal tumorigenesis.
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“Pancreatic, intestinal, and breast neoplasms were more frequently developed in rodents administered with incretin-based medications”
From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [57]
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“these results were not confirmed in human studies [56–58].”
From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [57]
Citations
Cites
Terzić, J., Grivennikov, S., Karin, E., & Karin, M. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.01.058 · Cited by 1,974
Mutations of Chromosome 5q21 Genes in FAP and Colorectal Cancer Patients
Nishisho, I., Nakamura, Y., Miyoshi, Y., Miki, Y., Ando, H., Horii, A., Koyama, K., Utsunomiya, J., Baba, S., Hedge, P., et al. (1991) · Science · doi:10.1126/science.1651563 · Cited by 1,891
Pharmacology, physiology, and mechanisms of incretin hormone action.
Campbell, J. E., & Drucker, D. J. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.008 · Cited by 1,500
Self-citationInduction of intestinal epithelial proliferation by glucagon-like peptide 2.
Drucker, D. J., Erlich, P., Asa, S. L., & Brubaker, P. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.15.7911 · Cited by 888
Self-citationPyke, C., Heller, R. S., Kirk, R. K., Ørskov, C., Reedtz-Runge, S., Kaastrup, P., Hvelplund, A., Bardram, L., Calatayud, D., & Knudsen, L. B. (2014) · Endocrinology · doi:10.1210/en.2013-1934 · Cited by 876 · cited 2×
“, 2014) and primates (Pyke et al., 2014), and FGF7 has been detected in the human ENS, raising the possibility that the ENS communicates a GLP-1R-dependent signal that converges on Fgf7 and ultimately promotes crypt fission.”
BackgroundCalle, E. E., & Thun, M. J. (2004) · Oncogene · doi:10.1038/sj.onc.1207751 · Cited by 805
Scrocchi, L. A., Brown, T. J., Maclusky, N., Brubaker, P. L., Auerbach, A. B., Joyner, A. L., & Drucker, D. J. (1996) · Nature Medicine · doi:10.1038/nm1196-1254 · Cited by 793
Self-citationSjöström, L., Gummesson, A., Sjöström, C. D., Narbro, K., Peltonen, M., Wedel, H., Bengtsson, C., Bouchard, C., Carlsson, B., Dahlgren, S., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70159-7 · Cited by 770
Modulation of Epithelial Cell Growth by Intraepithelial γδ T Cells
Boismenu, R., & Havran, W. L. (1994) · Science · doi:10.1126/science.7973709 · Cited by 652
Nilsson, R., Jain, M., Madhusudhan, N., Sheppard, N. G., Strittmatter, L., Kampf, C., Huang, J., Asplund, A., & Mootha, V. K. (2014) · Nature Communications · doi:10.1038/ncomms4128 · Cited by 607
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
Protection of the intestinal mucosa by intraepithelial γδ T cells
Chen, Y., Chou, K., Fuchs, E. V., Havran, W. L., & Boismenu, R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.212290499 · Cited by 481
Richards, P., Parker, H. E., Adriaenssens, A. E., Hodgson, J. M., Cork, S. C., Trapp, S., Gribble, F. M., & Reimann, F. (2014) · Diabetes · doi:10.2337/db13-1440 · Cited by 472
The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase.Preprint
Luetteke, N. C., Phillips, H. K., Qiu, T. H., Copeland, N. G., Earp, H. S., Jenkins, N. A., & Lee, D. C. (1994) · Genes & Development · doi:10.1101/gad.8.4.399 · Cited by 446
Asparagine Plays a Critical Role in Regulating Cellular Adaptation to Glutamine Depletion
Zhang, J., Fan, J., Venneti, S., Cross, J. R., Takagi, T., Bhinder, B., Djaballah, H., Kanai, M., Cheng, E. H., Judkins, A. R., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.018 · Cited by 439
Microbial Modulation of Energy Availability in the Colon Regulates Intestinal Transit
Wichmann, A., Allahyar, A., Greiner, T. U., Plovier, H., Östergren‐Lundén, G., Larsson, T. P., Drucker, D. J., Delzenne, N. M., Cani, P. D., & Bäckhed, F. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.09.012 · Cited by 380
Self-citationPanjwani, N., Mulvihill, E. E., Longuet, C., Yusta, B., Campbell, J. E., Brown, T. J., Streutker, C., Holland, D., Cao, X., Baggio, L. L., et al. (2013) · Endocrinology · doi:10.1210/en.2012-1937 · Cited by 346
Self-citationPhysiology and Pharmacology of the Enteroendocrine Hormone Glucagon-Like Peptide-2
Drucker, D. J., & Yusta, B. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170317 · Cited by 344
Self-citationMechanisms of changes in glucose metabolism and bodyweight after bariatric surgery
Madsbad, S., Dirksen, C., & Holst, J. J. (2014) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70218-3 · Cited by 307
Rodriguez‐Diaz, R., Dando, R., Jacques-Silva, M. C., Fachado, A., Molina, J., Abdulreda, M. H., Ricordi, C., Roper, S. D., Berggren, P., & Caicedo, A. (2011) · Nature Medicine · doi:10.1038/nm.2371 · Cited by 305
Greaves, L. C., Preston, S. L., Tadrous, P. J., Taylor, R. W., Barron, M. J., Oukrif, D., Leedham, S. J., Deheragoda, M. G., Sasieni, P. D., Novelli, M. R., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505903103 · Cited by 293
Regulation of the biological activity of glucagon-like peptide 2 in vivo by dipeptidyl peptidase IV
Drucker, D. J., Shi, Q., Crivici, A., Sumner-Smith, M., Tavares, W., Hill, M. E., DeForest, L., Cooper, S., & Brubaker, P. L. (1997) · Nature Biotechnology · doi:10.1038/nbt0797-673 · Cited by 278
Self-citationG-Protein-Coupled Receptors in Intestinal Chemosensation
Reimann, F. M., Tolhurst, G., & Gribble, F. M. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.019 · Cited by 245
Snippert, H. J. G., Schepers, A. G., van Es, J. H., Simons, B. D., & Clevers, H. C. (2013) · EMBO Reports · doi:10.1002/embr.201337799 · Cited by 239
Ørskov, C., Hartmann, B., Poulsen, S. S., Thulesen, J., Hare, K. J., & Holst, J. J. (2004) · Regulatory Peptides · doi:10.1016/j.regpep.2004.07.009 · Cited by 214
Dubé, P. E., Forse, C. L., Bahrami, J., & Brubaker, P. L. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.05.055 · Cited by 200
Self-citationPlamboeck, A., Veedfald, S., Deacon, C. F., Hartmann, B., Wettergren, A., Svendsen, L. B., Meisner, S., Hovendal, C. P., Vilsbøll, T., Knop, F. K., et al. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00035.2013 · Cited by 189
Lamont, B. J., Li, Y., Kwan, E. P., Brown, T. J., Gaisano, H. Y., & Drucker, D. J. (2011) · Journal of Clinical Investigation · doi:10.1172/jci42497 · Cited by 180
Self-citationControl of Insulin Secretion by Cholinergic Signaling in the Human Pancreatic Islet
Molina, J., Rodriguez‐Diaz, R., Fachado, A., Jacques-Silva, M. C., Berggren, P., & Caicedo, A. (2014) · Diabetes · doi:10.2337/db13-1371 · Cited by 164
Increased Risk of Colorectal Cancer After Obesity Surgery
Derogar, M., Hull, M. A., Kant, P., Östlund, M. P., Lu, Y., & Lagergren, J. (2013) · Annals of Surgery · doi:10.1097/sla.0b013e318288463a · Cited by 155
Ashrafian, H., Ahmed, K., Rowland, S. P., Patel, V., Gooderham, N. J., Holmes, E. C., Darzi, A. W., & Athanasiou, T. (2010) · Cancer · doi:10.1002/cncr.25738 · Cited by 150
ErbB Signaling Is Required for the Proliferative Actions of GLP-2 in the Murine Gut
Yusta, B., Holland, D. P., Koehler, J. A., Maziarz, M., Estall, J. L., Higgins, R. R., & Drucker, D. J. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.05.057 · Cited by 115
Self-citationDual elimination of the glucagon and GLP-1 receptors in mice reveals plasticity in the incretin axis
Ali, S., Lamont, B. J., Charron, M. J., & Drucker, D. J. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43615 · Cited by 111
Self-citationKissow, H., Hartmann, B., Holst, J. J., Viby, N., Gasbjerg, L. S., ROSENKILDE, M. M., Hare, K. J., & Poulsen, S. S. (2012) · Regulatory Peptides · doi:10.1016/j.regpep.2012.08.016 · Cited by 95
Sakthianandeswaren, A., Christie, M., D'Andreti, C., Tsui, C., Jorissen, R. N., Li, S., Fleming, N. I., Gibbs, P., Lipton, L. R., Malaterre, J., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2342 · Cited by 95
Madsen, K. B., Askov-Hansen, C., Naimi, R. M., Brandt, C. F., Hartmann, B., Holst, J. J., Mortensen, P. B., & Jeppesen, P. B. (2013) · Regulatory Peptides · doi:10.1016/j.regpep.2013.03.025 · Cited by 94
Rowland, K., Trivedi, S., Lee, D., Wan, K., Kulkarni, R., Holzenberger, M., & Brubaker, P. L. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.09.014 · Cited by 86
Self-citationLee, S., Lee, J., Li, K. K., Holland, D. P., Maughan, H., Guttman, D. S., Yusta, B., & Drucker, D. J. (2012) · Endocrinology · doi:10.1210/en.2011-1954 · Cited by 76
Self-citationAli, S., Ussher, J. R., Baggio, L. L., Kabir, M. G., Charron, M. J., Ilkayeva, O., Newgard, C. B., & Drucker, D. J. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.11.005 · Cited by 69
Self-citationLai, G. Y., Park, Y., Hartge, P. A., Hollenbeck, A. R., & Freedman, N. D. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3335 · Cited by 67
Plamboeck, A., Veedfald, S., Deacon, C. F., Hartmann, B., Wettergren, A., Svendsen, L. B., Meisner, S., Hovendal, C. P., Knop, F. K., Vilsbøll, T., et al. (2013) · European Journal of Endocrinology · doi:10.1530/eje-13-0264 · Cited by 59
Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats
Simonsen, L., Pilgaard, S., Ørskov, C., ROSENKILDE, M. M., Hartmann, B., Holst, J. J., & Deacon, C. F. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00453.2006 · Cited by 55
Kant, P., Sainsbury, A., Reed, K. R., Pollard, S. G., Scott, N., Clarke, A. R., Coletta, P. L., & Hull, M. A. (2011) · Gut · doi:10.1136/gut.2010.230755 · Cited by 51
Matsuda, Y., Ishiwata, T., Yamahatsu, K., Kawahara, K., Hagio, M., Peng, W., Yamamoto, T., Nakazawa, N., Seya, T., Ohaki, Y., et al. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.06.009 · Cited by 50
Watanabe, M., Ishiwata, T., Nishigai, K., Moriyama, Y., & Asano, G. (2000) · Pathology International · doi:10.1046/j.1440-1827.2000.01054.x · Cited by 50
Association Between Diagnosed Diabetes and Self-Reported Cancer Among U.S. Adults
Li, C., Balluz, L. S., Ford, E. S., Okoro, C. A., Tsai, J. H., & Zhao, G. (2011) · Diabetes Care · doi:10.2337/dc11-0020 · Cited by 45
Kedees, M. H., Guz, Y., Grigoryan, M., & Teitelman, G. (2013) · Peptides · doi:10.1016/j.peptides.2013.07.022 · Cited by 35
Regulation of Mouse Intestinal L Cell Progenitors Proliferation by the Glucagon Family of Peptides
Grigoryan, M., Kedees, M. H., Charron, M. J., Guz, Y., & Teitelman, G. (2012) · Endocrinology · doi:10.1210/en.2012-1120 · Cited by 34
Li, C.-F., He, H.-L., Wang, J., Huang, H.-Y., Wu, T., Hsing, C., Lee, S.-W., Lee, H.-H., Fang, J.-L., Huang, W.-T., et al. (2014) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2014-202551 · Cited by 30
Yoshino, M., Ishiwata, T., Watanabe, M., Komine, O., Shibuya, T., Tokunaga, A., & Naito, Z. (2005) · PubMed · Cited by 26
Expression of keratinocyte growth factor and its receptor in colorectal cancer
Otte, Schmitz, Banasiewicz, Drews, Fölsch, & Herzig (2000) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2000.00617.x · Cited by 25
Goodlad, R. A., Mandir, N., Meeran, K. M., Ghatei, M. A., Bloom, S. R., & Playford, R. J. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(99)00113-5 · Cited by 14
Pathuri, G., Li, Q., Mohammed, A., Gali, H., Pento, J. T., & Rao, C. V. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.01.042 · Cited by 6
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Metadata
- Authors
- Koehler, J. A., Baggio, L. L., Yusta, B., Longuet, C., Rowland, K. J., Cao, X., Holland, D., Brubaker, P. L., & Drucker, D. J.
- Affiliations
- Mount Sinai Hospital (CA)
- University of Toronto (CA)
- Corresponding author
- Drucker, Daniel J.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 21
- Issue
- 3
- Pages
- 379-391
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W1977144451
- Cited by
- 133
- References
- 53
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 10 · 2023: 9 · 2022: 9 · 2021: 18 · 2020: 11 · 2019: 9 · 2018: 13 · 2017: 6 · 2016: 14 · 2015: 8
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Park Service
- Intarcia Therapeutics
- Merck
- Canadian Institutes of Health Research (12344, MOP 123391)
- Novo Nordisk
- MedImmune
- Ariad Pharmaceuticals
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- GLP-1 receptor, glucagon-like peptide-1, FGF7, exendin-4, intestinal growth, intestinal polyps, intestinal tumorigenesis, ApcMin/+ mice, small intestine, colon, enteroendocrine L cells, incretin effect
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Exenatide, Glucagon-Like Peptide-1 Receptor Agonists, Animals, Colon, Epidermal Growth Factor, Female, Intestinal Mucosa, Intestine, Small, Male, Mice, Inbred C57BL, Peptides, Venoms, Signal Transduction, Receptor, IGF Type 1, Cell Proliferation, Mice, Fibroblast Growth Factor 7, Incretins, Carcinogenesis
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