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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In rodents, incretin-based medications were associated with more pancreatic, intestinal, and breast neoplasms.
“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]
Human studies did not confirm the rodent findings of increased pancreatic, intestinal, and breast neoplasms with incretin-based medications.
“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]
Cites
Terzić, J., Grivennikov, S., Karin, E., & Karin, M. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.01.058 · Cited by 1,974 · see citing works
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 · see citing works
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 · see citing works
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 880 · see citing works
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× · see citing works
“, 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.”
BackgroundScrocchi, 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 · see citing works
Self-citationCalle, E. E., & Thun, M. J. (2004) · Oncogene · doi:10.1038/sj.onc.1207751 · Cited by 791 · see citing works
Sjöström, 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 · see citing works
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 · see citing works
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 · 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
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 480 · see citing works
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 · see citing works
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 · see citing works
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 438 · see citing works
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 382 · see citing works
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 · see citing works
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 · see citing works
Self-citationRodriguez‐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 · see citing works
Mechanisms 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 299 · see citing works
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 · see citing works
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 · see citing works
Self-citationSnippert, 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 · see citing works
G-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 235 · see citing works
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 · see citing works
Dubé, P. E., Forse, C. L., Bahrami, J., & Brubaker, P. L. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.05.055 · Cited by 200 · see citing works
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 183 · see citing works
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 171 · see citing works
Self-citationIncreased 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 · see citing works
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 149 · see citing works
Control of Insulin Secretion by Cholinergic Signaling in the Human Pancreatic Islet
Molina, J., Rodriguez-Diaz, R., Fachado, A., Jacques-Silva, M. C., Berggren, P.-O., & Caicedo, A. (2014) · Diabetes · doi:10.2337/db13-1371 · Cited by 149 · see citing works
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 · see citing works
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 109 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 68 · see citing works
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 58 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Kedees, M. H., Guz, Y., Grigoryan, M., & Teitelman, G. (2013) · Peptides · doi:10.1016/j.peptides.2013.07.022 · Cited by 35 · see citing works
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 · see citing works
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 · see citing works
Yoshino, M., Ishiwata, T., Watanabe, M., Komine, O., Shibuya, T., Tokunaga, A., & Naito, Z. (2005) · PubMed · Cited by 26 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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Drucker, D. J. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.001 · Cited by 2,170 · see citing works
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Beumer, J., & Clevers, H. C. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0278-0 · Cited by 676 · see citing works
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Drucker, D. J. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.06.009 · Cited by 665 · see citing works
Self-citationDiscovery, characterization, and clinical development of the glucagon-like peptides
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Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand?
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Pharmacotherapy of obesity: available medications and drugs under investigation.
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Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion
Lebrun, L. J., Lenaerts, K., Kiers, D., Pais de Barros, J.-P., Le Guern, N., Plesnik, J., Thomas, C., Bourgeois, T., Dejong, C. H. C., Kox, M., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.008 · Cited by 238 · see citing works
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Lund, M. L., Sorrentino, G., Egerod, K. L., Kroone, C., Mortensen, B., Knop, F. K., Reimann, F. M., Gribble, F. M., Drucker, D. J., de Koning, E. J. P., et al. (2020) · Diabetes · doi:10.2337/db19-0764 · Cited by 82 · see citing works
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Hvistendahl, M., Brandt, C. F., Tribler, S., Naimi, R. M., Hartmann, B., Holst, J. J., Rehfeld, J. F., Hornum, M., Andersen, J. R., Henriksen, B. M., et al. (2016) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607116672265 · Cited by 75 · see citing works
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Hunt, J. E., Holst, J. J., Jeppesen, P. B., & Kissow, H. (2021) · Biomedicines · doi:10.3390/biomedicines9040383 · Cited by 65 · see citing works
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The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer
Ibrahim, S. S., Ibrahim, R. S., Arabi, B., Brockmueller, A., Shakibaei, M., & Büsselberg, D. (2024) · Cancer and Metastasis Reviews · doi:10.1007/s10555-024-10192-9 · Cited by 56 · see citing works
Lin, A., Ding, Y., Li, Z., Jiang, A., Liu, Z., Wong, H. Z. H., Cheng, Q., Zhang, J., & Luo, P. (2025) · Biomarker Research · doi:10.1186/s40364-025-00765-3 · Cited by 53 · see citing works
Figlioli, G., Piovani, D., Peppas, S., Pugliese, N., Hassan, C., Repici, A., Lleò, A., Aghemo, A., & Bonovas, S. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107401 · Cited by 52 · see citing works
Hicks, B. M., Yin, H., Yu, O. H. Y., Pollak, M., Platt, R. W., & Azoulay, L. (2016) · BMJ · doi:10.1136/bmj.i5340 · Cited by 53 · see citing works
Incretin-based therapies: where will we be 50 years from now?
Meier, J. J., & Nauck, M. A. (2015) · Diabetologia · doi:10.1007/s00125-015-3608-6 · Cited by 52 · see citing works
The Distal Predilection of Small Bowel Neuroendocrine Tumors
Keck, K. J., Maxwell, J. E., Utria, A. F., Bellizzi, A. M., Dillon, J. S., O’Dorisio, T. M., & Howe, J. R. (2018) · Annals of Surgical Oncology · doi:10.1245/s10434-018-6676-2 · Cited by 51 · see citing works
Ding, W., Chang, W., Guo, X.-C., Liu, Y., Xiao, D., Ding, D., Wang, J., & Zhang, X. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00202 · Cited by 50 · see citing works
The regulation of function, growth and survival of GLP-1-producing L-cells
Kuhre, R. E., Holst, J. J., & Krizhanovskii, C. (2015) · Clinical Science · doi:10.1042/cs20150154 · Cited by 48 · see citing works
Vekić, J., Zeljković, A., Stefanović, A., Giglio, R. V., Ciaccio, M., & Rizzo, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212409 · Cited by 46 · see citing works
Liu, Z., Duan, X., Yuan, M., Yu, J. Y., Hu, X., Han, X., Lan, L., Liu, B., Wang, Y., & Qin, J. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120370 · Cited by 45 · see citing works
The endogenous preproglucagon system is not essential for gut growth homeostasis in mice
Wismann, P., Barkholt, P., Secher, T., Vrang, N., Hansen, H. B., Jeppesen, P. B., Baggio, L. L., Koehler, J. A., Drucker, D. J., Sandoval, D. A., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.04.007 · Cited by 43 · see citing works
Self-citationReiner, J., Berlin, P., Held, J., Thiery, J., Skarbaliene, J., Griffin, J., Russell, W., Eriksson, P., Berner-Hansen, M. A., Ehlers, L., et al. (2021) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2286 · Cited by 43 · see citing works
Wismann, P., Pedersen, S. L., Hansen, G., Mannerstedt, K., Pedersen, P. J., Jeppesen, P. B., Vrang, N., Fosgerau, K., & Jelsing, J. (2018) · Physiology & Behavior · doi:10.1016/j.physbeh.2018.03.004 · Cited by 43 · see citing works
Peiris, M., Aktar, R., Reed, D. E., Cibert‐Goton, V., Zdanaviciene, A., Halder, W., Robinow, A. D., Corke, S., Dogra, H., Knowles, C. H., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-323219 · Cited by 40 · see citing works
Morrow, N. M., Trzaskalski, N. A., Hanson, A. A., Fadzeyeva, E., Telford, D. E., Chhoker, S. S., Sutherland, B. G., Edwards, J. Y., Huff, M. W., & Mulvihill, E. E. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.316896 · Cited by 40 · see citing works
Arvanitakis, K., Koufakis, T., Popovic, D. S., Maltese, G., Mustafa, O. G., Doumas, M. N., Γιουλεμέ, Ό., Kotsa, K., & Germanidis, G. S. (2023) · Current Obesity Reports · doi:10.1007/s13679-023-00506-3 · Cited by 37 · see citing works
The gut hormone receptor GIPR links energy availability to the control of hematopoiesis
Pujadas, G., Varin, E. M., Baggio, L. L., Mulvihill, E. E., Bang, K. W. A., Koehler, J. A., Matthews, D., & Drucker, D. J. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101008 · Cited by 35 · see citing works
Self-citationRathmann, W., & Kostev, K. (2017) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2017.01.012 · Cited by 34 · see citing works
Hytting-Andreasen, R., Balk-Møller, E., Hartmann, B., Pedersen, J., Windeløv, J. A., Holst, J. J., & Kissow, H. (2018) · PLoS ONE · doi:10.1371/journal.pone.0198046 · Cited by 33 · see citing works
Unintended Effects of GPCR-Targeted Drugs on the Cancer Phenotype
Cornwell, A. C., & Feigin, M. E. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.10.001 · Cited by 33 · see citing works
Oliveira, F. C. B., Bauer, E. J., Ribeiro, C. M., Pereira, S. A., Beserra, B. T. S., Wajner, S. M., Maia, A. L., Neves, F. A. R., Coelho, M. S., & Amato, A. A. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.803363 · Cited by 30 · see citing works
Mulvihill, E. E. (2018) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000495 · Cited by 29 · see citing works
Incretin-based Drugs and the Incidence of Colorectal Cancer in Patients with Type 2 Diabetes
Abrahami, D., Yin, H., Yu, O. H. Y., Pollak, M., & Azoulay, L. (2017) · Epidemiology · doi:10.1097/ede.0000000000000793 · Cited by 30 · see citing works
Liu, H., Hong, Y., Chen, H., Wang, X., Dong, J., Li, X., Shi, Z., Zhao, Q., Zhou, L., Wang, J., et al. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.11.017 · Cited by 26 · see citing works
Glucagon‐like Peptide‐2 and the Regulation of Intestinal Growth and Function
Brubaker, P. L. (2018) · Comprehensive physiology · doi:10.1002/j.2040-4603.2018.tb00039.x · Cited by 26 · see citing works
Self-citationPatel, A. R., Yusta, B., Matthews, D., Charron, M. J., Seeley, R. J., & Drucker, D. J. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.06.006 · Cited by 25 · see citing works
Self-citationHtoo, P. T., Buse, J. B., Gokhale, M., Marquis, M. A., Pate, V., & Stürmer, T. (2016) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-016-2068-3 · Cited by 25 · see citing works
Reiner, J., Thiery, J., Held, J., Berlin, P., Skarbaliene, J., Vollmar, B., Jaster, R., Eriksson, P., Lamprecht, G., & Witte, M. (2022) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14791 · Cited by 24 · see citing works
Effects of semaglutide on metabolism and gut microbiota in high-fat diet-induced obese mice
Sun, L., Shang, B., Lv, S., Liu, G., Wu, Q., & Geng, Y. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1562896 · Cited by 25 · see citing works
The role of fibroblast growth factor 7 in cartilage development and diseases.
Zhang, X.-Y., Pu, X., Pi, C.-X., & Xie, J. (2023) · Life Science · doi:10.1016/j.lfs.2023.121804 · Cited by 21 · see citing works
Glucose-dependent insulinotropic polypeptide receptor signaling alleviates gut inflammation in mice
Hammoud, R., Kaur, K. D., Koehler, J. A., Baggio, L. L., Wong, C. K., Advani, K. E., Yusta, B., Efimova, I., Gribble, F. M., Reimann, F., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.174825 · Cited by 24 · see citing works
Self-citationMartchenko, S. E., Martchenko, A., Biancolin, A. D., Waller, A. S., & Brubaker, P. L. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101340 · Cited by 20 · see citing works
Self-citationRepurposing glucose-lowering drugs for cancer therapy
Luconi, M., Cantini, G., & Crescioli, C. (2025) · Trends in cancer · doi:10.1016/j.trecan.2025.04.010 · Cited by 19 · see citing works
Is there an association between liraglutide use and female breast cancer in a real-world setting?
Funch, D. P., Mortimer, K., Li, L., Norman, H. S., Major‐Pedersen, A., Olsen, A. H., Kaltoft, M. S., & Dore, D. D. (2018) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s171503 · Cited by 18 · see citing works
Kuo, C.-C., Chuang, M., Li, C., Tsai, Y., Huang, P., Kuo, H., & Lai, C.-C. (2025) · Diabetologia · doi:10.1007/s00125-025-06453-z · Cited by 18 · see citing works
Crosstalk between incretin hormones, Th17 and Treg cells in inflammatory diseases
da Silva, E. M., Yariwake, V. Y., Alves, R. W., de Araújo, D. R., & Andrade‐Oliveira, V. (2022) · Peptides · doi:10.1016/j.peptides.2022.170834 · Cited by 18 · see citing works
Morrow, N. M., Hanson, A. A., & Mulvihill, E. E. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.703966 · Cited by 17 · see citing works
Merlo, F. D., Aimasso, U., Ossola, M., Ippolito, M., Cravero, L., Ponzo, V., & Bo, S. (2023) · Nutrients · doi:10.3390/nu15122740 · Cited by 16 · see citing works
Mahdy, R. N. E., Nader, M. A., Helal, M., Abu-Risha, S. E., & Abdelmageed, M. E. (2024) · Naunyn-Schmiedeberg's Archives of Pharmacology · doi:10.1007/s00210-024-03631-5 · Cited by 17 · see citing works
Yabe, D., Kuwata, H., Usui, R., Kurose, T., & Seino, Y. (2015) · Current Medical Research and Opinion · doi:10.1185/03007995.2015.1045471 · Cited by 16 · see citing works
Jeffrey, L. O. (2019) · Clinical Medical Reviews and Case Reports · doi:10.23937/2378-3656/1410281 · Cited by 16 · see citing works
GLP-1 receptor agonists in IBD: exploring the crossroads of metabolism and inflammation
Migliorisi, G., Gabbiadini, R., Buono, A. D., Ferraris, M., Privitera, G., Petronio, L., Bertoli, P., Bezzio, C., & Armuzzi, A. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1610368 · Cited by 15 · see citing works
Greiner, T. U., Koh, A., Peris, E., Bergentall, M., Johansson, M., Hansson, G. C., Drucker, D. J., & Bäckhed, F. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.101924 · Cited by 15 · see citing works
Self-citationEbbesen, M., Kissow, H., Hartmann, B., Grell, K., Gørløv, J. S., Kielsen, K., Holst, J. J., & Müller, K. (2019) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2019.01.036 · Cited by 14 · see citing works
Martchenko, S. E., Sweeney, M. E., Dimitriadou, V., Murray, J. A., & Brubaker, P. L. (2020) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.119.263947 · Cited by 14 · see citing works
Self-citationQin, S., Bai, W., Applegate, T. J., Zhang, K., Tian, G., Ding, X., Bai, S., Wang, J., Lv, L., Peng, H., et al. (2022) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-022-00735-x · Cited by 13 · see citing works
Tambo, A., Roshan, M. H. K., & Pace, N. P. (2016) · International Journal of Chronic Diseases · doi:10.1155/2016/7030795 · Cited by 13 · see citing works
Canagliflozin Increases Intestinal Adenoma Burden in Female ApcMin/+ Mice
Korfhage, J. L., Skinner, M. E., Basu, J., Greenson, J. K., Miller, R. A., & Lombard, D. B. (2021) · The Journals of Gerontology Series A · doi:10.1093/gerona/glab254 · Cited by 12 · see citing works
Martchenko, S. E., Prescott, D., Martchenko, A., Sweeney, M. E., Philpott, D. J., & Brubaker, P. L. (2021) · Scientific Reports · doi:10.1038/s41598-021-98986-7 · Cited by 12 · see citing works
Self-citationGlucagon-like peptide-1 medicines and cancer
Yabut, J. M., & Drucker, D. J. (2026) · Nature Cancer · doi:10.1038/s43018-025-01110-1 · Cited by 11 · see citing works
Self-citationGLP-1 receptor agonist as treatment for cancer as well as diabetes: beyond blood glucose control
Nomiyama, T., & Yanase, T. (2016) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2016.1191349 · Cited by 11 · see citing works
Sørum, M. E., Kissow, H., Hartmann, B., Kielsen, K., Sørensen, K., Stinson, S. E., Frithioff‐Bøjsøe, C., Fonvig, C. E., Holm, J., Hansen, T. F., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.793588 · Cited by 11 · see citing works
Hepprich, M., Antwi, K., Waser, B., Reubi, J., Wild, D., & Christ, E. (2020) · Case Reports in Endocrinology · doi:10.1155/2020/4510910 · Cited by 8 · see citing works
Chen, B., Zhou, W., Zhao, W., Yuan, P., Tang, C., Wang, G., Leng, J., Ma, J., Wang, X., Hui, Y., et al. (2019) · Oncology Letters · doi:10.3892/ol.2019.10497 · Cited by 10 · see citing works
Hashimoto Takigami, N., Kuniyoshi, S., Miki, Y., Tamaki, K., Kamada, Y., Uehara, K., Tsuchiya, S., Terukina, S., Iwabuchi, E., Kanai, A., et al. (2021) · Breast Cancer Research and Treatment · doi:10.1007/s10549-021-06288-3 · Cited by 10 · see citing works
Building better barriers: how nutrition and undernutrition impact pediatric intestinal health
Andres, S. F., Zhang, Y., Kuhn, M. R., & Scottoline, B. P. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1192936 · Cited by 10 · see citing works
Zhong, Y., Wu, T., & Khan, N. U. (2025) · BMC Gastroenterology · doi:10.1186/s12876-025-04211-4 · Cited by 8 · see citing works
Srikrishnaraj, A., Jeong, H., & Brubaker, P. L. (2021) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2307 · Cited by 8 · see citing works
Self-citationMorrow, N. M., Locatelli, C. A. A., Trzaskalski, N. A., Klein, C. T., Hanson, A. A., Al-Hadi, H., Tripathi, I., Clément, A. C., Imran, S., Lorenzen‐Schmidt, I., et al. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2022.159208 · Cited by 8 · see citing works
An Innate Disposition for a Healthier Gut: GLP-1R Signaling in Intestinal Epithelial Lymphocytes
Rosario, W., & D’Alessio, D. D. (2015) · Diabetes · doi:10.2337/db15-0436 · Cited by 8 · see citing works
Karp, I., Sivaswamy, A., & Booth, C. M. (2019) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.4746 · Cited by 8 · see citing works
Sørum, M. E., Gang, A. O., Tholstrup, D., Gudbrandsdottir, S., Kissow, H., Kornblit, B. T., Müller, K., & Knop, F. K. (2024) · BMJ Open · doi:10.1136/bmjopen-2024-089862 · Cited by 7 · see citing works
Smoke or Fire? Acute Pancreatitis and the Liraglutide Trials
Gale, E. A. (2015) · Diabetes Care · doi:10.2337/dc15-0346 · Cited by 7 · see citing works
Glucagon-like peptide-1 receptor agonists and risk of breast cancer
Bolen, S. D., & Maruthur, N. M. (2016) · BMJ · doi:10.1136/bmj.i5519 · Cited by 7 · see citing works
Du, W., Miao, Y., Zhang, G., Luo, G.-C., Yang, P., Chen, F., Zhang, B., Yang, C., Li, G., & Chang, J. (2022) · Disease Markers · doi:10.1155/2022/4262600 · Cited by 6 · see citing works
Fitzgerald, D. M., Cash, C. M., Dudley, K. J., Sibthorpe, P. E. M., Sillence, M. N., & de Laat, M. A. (2023) · Equine Veterinary Journal · doi:10.1111/evj.14020 · Cited by 6 · see citing works
Indole-3-carboxyaldehyde does not reverse the intestinal effects of fiber-free diet in mice
Smits, M. M., Dreyer, S. I. L., Hunt, J. E., Drzazga, A. K., Modvig, I. M., Holst, J. J., & Kissow, H. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1362711 · Cited by 6 · see citing works
- 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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