The bile acid TUDCA increases glucose-induced insulin secretion via the cAMP/PKA pathway in pancreatic beta cells
Open accessAbstract
Objective While bile acids are important for the digestion process, they also act as signaling molecules in many tissues, including the endocrine pancreas, which expresses specific bile acid receptors that regulate several cell functions. In this study, we investigated the effects of the conjugated bile acid TUDCA on glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells.Methods Pancreatic islets were isolated from 90-day-old male mice. Insulin secretion was measured by radioimmunoassay, protein phosphorylation by western blot, Ca(2+) signals by fluorescence microscopy and ATP-dependent K(+) (KATP) channels by electrophysiology.Results TUDCA dose-dependently increased GSIS in fresh islets at stimulatory glucose concentrations but remained without effect at low glucose levels. This effect was not associated with changes in glucose metabolism, Ca(2+) signals or KATP channel activity; however, it was lost in the presence of a cAMP competitor or a PKA inhibitor. Additionally, PKA and CREB phosphorylation were observed after 1-hour incubation with TUDCA. The potentiation of GSIS was blunted by the Gα stimulatory, G protein subunit-specific inhibitor NF449 and mimicked by the specific TGR5 agonist INT-777, pointing to the involvement of the bile acid G protein-coupled receptor TGR5.Conclusion Our data indicate that TUDCA potentiates GSIS through the cAMP/PKA pathway.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Bile acids induce insulin secretion directly via the transmembrane bile acid receptor Takeda G protein-coupled receptor 5 on β cells and indirectly via stimulation of L-cell derived GLP-1 and subsequent insulin release.
“Bile acids induce insulin secretion directly via the transmembrane bile acid receptor Takeda G protein–coupled receptor 5 (on β cells and indirectly via stimulation of l-cell derived GLP-1 and subsequent insulin release (110–112).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [111]
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Özcan, U., Yilmaz, E., Özcan, L., Furuhashi, M., Vaillancourt, E., Smith, R. O., Görgün, C. Z., & Hotamisligil, G. S. (2006) · Science · doi:10.1126/science.1128294 · Cited by 2,413 · see citing works
Targeting bile‐acid signalling for metabolic diseases
Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J., & Schoonjans, K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2619 · Cited by 1,422 · see citing works
Bile Acid Metabolism and Signaling
Chiang, J. Y. L. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120023 · Cited by 1,390 · see citing works
Pleiotropic Roles of Bile Acids in Metabolism
de Aguiar Vallim, T. Q., Tarling, E. J., & Edwards, P. A. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.013 · Cited by 1,209 · see citing works
Mudaliar, S., Henry, R. R., Sanyal, A. J., Morrow, L., Marschall, H., Kipnes, M., Adorini, L., Sciacca, C. I., Clopton, P., Castelloe, E., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.05.042 · Cited by 931 · see citing works
Katsuma, S., Hirasawa, A., & Tsujimoto, G. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.01.139 · Cited by 789 · see citing works
Eto, K., Tsubamoto, Y., Terauchi, Y., 杉山, 拓., Kishimoto, T. E., Takahashi, N. K., Yamauchi, N., Kubota, N., Murayama, S., Aizawa, T., et al. (1999) · Science · doi:10.1126/science.283.5404.981 · Cited by 491 · see citing works
The bile acid TGR5 membrane receptor: from basic research to clinical application
Duboc, H., Taché, Y., & Hofmann, A. F. (2014) · Digestive and Liver Disease · doi:10.1016/j.dld.2013.10.021 · Cited by 473 · see citing works
Cipriani, S., Mencarelli, A., Palladino, G., & Fiorucci, S. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m001602 · Cited by 410 · see citing works
Bile acids: regulation of apoptosis by ursodeoxycholic acid
Amaral, J. D., Viana, R. J. S., Ramalho, R. M., Steer, C. J., & Rodrigues, C. M. P. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r900011-jlr200 · Cited by 360 · see citing works
Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea
Sato, H., Genet, C., Strehle, A., Thomas, C., Lobstein, A., Wagner, A., Mioskowski, C., Auwerx, J. H., & Saladin, R. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.06.130 · Cited by 341 · see citing works
Carrasco, A. J., Dzeja, P. P., Alekseev, A. E., Pucar, D., Zingman, L. V., Abraham, M. R., Hodgson, D. M., Bienengraeber, M., Pucéat, M., Janssen, E., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121038198 · Cited by 238 · see citing works
Schoemaker, M. H., de la Rosa, L. C., Buist-Homan, M., Vrenken, T. E., Havinga, R., Poelstra, K., Haisma, H. J., Jansen, P. L. M., & Moshage, H. (2004) · Hepatology · doi:10.1002/hep.20246 · Cited by 229 · see citing works
Kumar, D. P., Rajagopal, S., Mahavadi, S., Mirshahi, F., Grider, J. R., Murthy, K. S., & Sanyal, A. J. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.09.104 · Cited by 206 · see citing works
The Unexpected Uses of Urso- and Tauroursodeoxycholic Acid in the Treatment of Non-liver Diseases
Vang, S., Longley, K., Steer, C. J., & Low, W. C. (2014) · Global Advances in Health and Medicine · doi:10.7453/gahmj.2014.017 · Cited by 202 · see citing works
The bile acid sensor FXR regulates insulin transcription and secretion
Renga, B., Mencarelli, A., Vavassori, P., Brancaleone, V., & Fiorucci, S. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.01.002 · Cited by 189 · see citing works
The bile acid membrane receptor TGR5: a valuable metabolic target
Pols, T. W. H., Noriega, L. G., Nomura, M., Auwerx, J., & Schoonjans, K. (2011) · Digestive Diseases · doi:10.1159/000324126 · Cited by 185 · see citing works
Düfer, M., Hörth, K., Wagner, R., Schittenhelm, B., Prowald, S., Wagner, T. F. J., Oberwinkler, J., Łukowski, R., Gonzalez, F. J., Krippeit‐Drews, P., et al. (2012) · Diabetes · doi:10.2337/db11-0815 · Cited by 160 · see citing works
Taurine supplementation modulates glucose homeostasis and islet function
Carneiro, E. M., Latorraca, M. Q., ARAUJO, E. P. D., Beltrá, M., Oliveras‐López, M., Navarro, M., Berná, G., Bedoya, F. J., Velloso, L. A., Soria, B., et al. (2008) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2008.05.008 · Cited by 146 · see citing works
Self-citationGlucagon-like peptide-1: a major regulator of pancreatic beta-cell function
Perfetti, R., & Merkel, P. A. (2000) · European Journal of Endocrinology · doi:10.1530/eje.0.1430717 · Cited by 143 · see citing works
Bile acid stimulates hepatocyte polarization through a cAMP-Epac-MEK-LKB1-AMPK pathway
Fu, D., Wakabayashi, Y., Lippincott‐Schwartz, J., & Arias, I. M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018376108 · Cited by 141 · see citing works
Bala, V., Rajagopal, S., Kumar, D. P., Nalli, A. D., Mahavadi, S., Sanyal, A. J., Grider, J. R., & Murthy, K. S. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00420 · Cited by 124 · see citing works
Tauroursodeoxycholate (TUDCA), chemical chaperone, enhances function of islets by reducing ER stress
Lee, Y. Y., Hong, S. H., Lee, Y. J., Chung, S. S., Jung, H. S., Park, S. G., & Park, K. S. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.06.022 · Cited by 113 · see citing works
Snapin Mediates Incretin Action and Augments Glucose-Dependent Insulin Secretion
Song, W., Seshadri, M. R., Ashraf, U., Mdluli, T., Mondal, P., Keil, M. F., Azevedo, M. F., Kirschner, L. S., Stratakis, C. A., & Hussain, M. A. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.02.002 · Cited by 113 · see citing works
Neuro-humoral signalling by bile acids and the TGR5 receptor in the gastrointestinal tract
Bunnett, N. W. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.271155 · Cited by 110 · see citing works
Sepe, V., Renga, B., Festa, C., D’Amore, C., Masullo, D., Cipriani, S., Leva, F. S. D., Monti, M. C., Novellino, E., Limongelli, V., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500889f · Cited by 88 · see citing works
Rafacho, A., Marroquí, L., Taboga, S. R., Abrantes, J. L. F., Silveira, L. R., Boschero, A. C., Carneiro, E. M., Bosqueiro, J. R., Nadal, A., & Quesada, I. (2010) · Endocrinology · doi:10.1210/en.2009-0704 · Cited by 80 · see citing works
Self-citationIonic mechanisms involved in the regulation of insulin secretion by muscarinic agonists
Bordin, S., Boschero, A. C., Carneiro, E. M., & Atwater, I. (1995) · The Journal of Membrane Biology · doi:10.1007/bf00207273 · Cited by 67 · see citing works
Self-citationValdeolmillos, M., Nadal, A., Contreras, D., & Soria, B. (1992) · Journal of Physiology · doi:10.1113/jphysiol.1992.sp019295 · Cited by 66 · see citing works
Self-citationNakajima, T., Okuda, Y., Chisaki, K., Shin, W. S., Iwasawa, K., Morita, T., Matsumoto, A., Suzuki, J., Suzuki, S., Yamada, N., et al. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703471 · Cited by 64 · see citing works
Halim, V. A., Álvarez‐Fernández, M., Xu, Y. J., Aprelia, M., van den Toorn, H., Heck, A. J. R., Mohammed, S., & Medema, R. H. (2013) · Science Signaling · doi:10.1126/scisignal.2003664 · Cited by 61 · see citing works
Cooperation between cAMP signalling and sulfonylurea in insulin secretion
Shibasaki, T., Takahashi, T., Takahashi, H., & Seino, S. (2014) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12343 · Cited by 43 · see citing works
Effects of Chemical Modification of Ursodeoxycholic Acid on TGR5 Activation
Iguchi, Y., Nishimaki‐Mogami, T., Yamaguchi, M., Teraoka, F., Kaneko, T., & Une, M. (2011) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.34.1 · Cited by 42 · see citing works
Henquin, J.-C., & Nenquin, M. (2014) · Endocrinology · doi:10.1210/en.2014-1247 · Cited by 41 · see citing works
Spatial Control of Epac2 Activity by cAMP and Ca2+-Mediated Activation of Ras in Pancreatic β Cells
Idevall-Hagren, O., Jakobsson, I., Xu, Y., & Tengholm, A. (2013) · Science Signaling · doi:10.1126/scisignal.2003932 · Cited by 38 · see citing works
Soriano, S., Gonzalez, A., Marroquí, L., Tudurí, E., Vieira, E., Amaral, A. G., Batista, T. M., Rafacho, A., Boschero, A. C., Nadal, A., et al. (2010) · Endocrinology · doi:10.1210/en.2010-0008 · Cited by 38 · see citing works
Self-citation
Flagged first, then by citations
1 of the 38 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00211 · Cited by 787 · see citing works
Fleishman, J. S., & Kumar, S. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01811-6 · Cited by 577 · see citing works
Bile acids in glucose metabolism and insulin signalling — mechanisms and research needs
Ahmad, T. R., & Haeusler, R. A. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0266-7 · Cited by 342 · see citing works
Drug-microbiota interactions: an emerging priority for precision medicine
Zhao, Q. C., Chen, Y., Huang, W., Zhou, H., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01619-w · Cited by 296 · see citing works
Kusaczuk, M. (2019) · Cells · doi:10.3390/cells8121471 · Cited by 244 · see citing works
Xiao, H., Yan, J., Huang, L., Araujo, C., Peng, J., Gao, L., Liu, S., Tang, J., Zuo, G., & Zhang, J. H. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.09.016 · Cited by 180 · see citing works
Zhao, L., Chen, Y., Xia, F., Abudukerimu, B., Zhang, W., Guo, Y., Wang, N., & Lu, Y. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00233 · Cited by 153 · see citing works
Bile acids and bariatric surgery
Albaugh, V. L., Banan, B., Ajouz, H., Abumrad, N. N., & Flynn, C. R. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.04.001 · Cited by 148 · see citing works
The bile acid TUDCA and neurodegenerative disorders: An overview
Zangerolamo, L., Vettorazzi, J. F., Rosa, L. R. D. O., Carneiro, E. M., & Barbosa, H. C. L. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119252 · Cited by 127 · see citing works
Self-citationMechanism of action of the bile acid receptor TGR5 in obesity
Lun, W., Yan, Q., Guo, X., Zhou, M., Bai, Y., He, J., Cao, H., Che, Q., Guo, J., & Su, Z. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.11.011 · Cited by 117 · see citing works
Kaska, Ł., Śledziński, T., Chomiczewska, A., Dettlaff‐Pokora, A., & Świerczyński, J. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i39.8698 · Cited by 111 · see citing works
Zuo, G., Zhang, T., Huang, L., Araujo, C., Peng, J., Travis, Z. D., Okada, T., Ocak, U., Zhang, G., Tang, J., et al. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.09.002 · Cited by 102 · see citing works
Rafiee, Z., García-Serrano, A. M., & Duarte, J. M. N. (2022) · Nutrients · doi:10.3390/nu14061292 · Cited by 100 · see citing works
From role of gut microbiota to microbial-based therapies in type 2-diabetes
Leylabadlo, H. E., Sanaie, S., Heravi, F. S., Ahmadian, Z., & Ghotaslou, R. (2020) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2020.104268 · Cited by 92 · see citing works
Gut and obesity/metabolic disease: Focus on microbiota metabolites
Lin, K., Zhu, L., & Li, Y. (2022) · MedComm · doi:10.1002/mco2.171 · Cited by 95 · see citing works
ASBT(SLC10A2): A promising target for treatment of diseases and drug discovery
Yang, N., Dong, Y., Jia, G., Fan, S., Li, S.-Z., Yang, S., & Li, Y. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110835 · Cited by 85 · see citing works
Zhu, H., Wang, G., Nguyen-Ngoc, K.-V., Kim, D., Miller, M., Goss, G., Kovsky, J., Harrington, A. R., Saunders, D. C., Hopkirk, A. L., et al. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.03.011 · Cited by 85 · see citing works
Crosstalk between gut microbiota and antidiabetic drug action
Kyriachenko, Y., Falalyeyeva, T. M., Korotkyi, O., Molochek, N., & Kobyliak, N. M. (2019) · World Journal of Diabetes · doi:10.4239/wjd.v10.i3.154 · Cited by 82 · see citing works
Sarkar, P., Basak, P., Ghosh, S., Kundu, M., & Sil, P. C. (2017) · Food and Chemical Toxicology · doi:10.1016/j.fct.2017.10.022 · Cited by 77 · see citing works
Maczewsky, J., Kaiser, J., Gresch, A., Gerst, F., Düfer, M., Krippeit‐Drews, P., & Drews, G. (2018) · Diabetes · doi:10.2337/db18-0315 · Cited by 66 · see citing works
Zangerolamo, L., Vettorazzi, J. F., Solon, C., Bronczek, G. A., Engel, D. F., Kurauti, M. A., Soares, G. M., Rodrigues, K. S., Velloso, L. A., Boschero, A. C., et al. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.111116 · Cited by 66 · see citing works
Self-citationRani, S., Sreenivasaiah, P. K., Kim, J. O., Lee, M. Y., Kang, W. S., Kim, Y. S., Ahn, Y., Park, W. J., Cho, C., & Kim, D. H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0176071 · Cited by 63 · see citing works
Liu, W., Luo, Z., Zhou, J., & Sun, B. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.853771 · Cited by 62 · see citing works
Bile acids and their effects on diabetes
Rajani, C., & Jia, W. P. (2018) · Frontiers of Medicine · doi:10.1007/s11684-018-0644-x · Cited by 61 · see citing works
Bronczek, G. A., Vettorazzi, J. F., Soares, G. M., Kurauti, M. A., dos Santos, C., Bonfim, M. F., Carneiro, E. M., Balbo, S. L., Boschero, A. C., & Júnior, J. M. C. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00561 · Cited by 57 · see citing works
Self-citationResearch progress on the relationship between bile acid metabolism and type 2 diabetes mellitus
Hou, Y., Zhai, X., Wang, X., Wu, Y., Wang, H., Qin, Y., Han, J., & Meng, Y. (2023) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-023-01207-6 · Cited by 55 · see citing works
Vettorazzi, J. F., Kurauti, M. A., Soares, G. M., Borck, P. C., Ferreira, S. M., Branco, R. C. S., Michelone, L. D. S. L., Boschero, A. C., Costa, J. M., & Carneiro, E. M. (2017) · Scientific Reports · doi:10.1038/s41598-017-13974-0 · Cited by 54 · see citing works
Self-citationBasso, N., Soricelli, E., Castagneto-Gissey, L., Casella, G., Albanese, D., Fava, F., Donati, C., Tuohy, K., Angelini, G., La Neve, F., et al. (2016) · Diabetes · doi:10.2337/db16-0039 · Cited by 53 · see citing works
Şak, D., Erdenen, F., Müderrisoğlu, C., Altunoğlu, E., Sözer, V., Güngel, H., Güler, P. A., Şak, T., & Uzun, H. (2019) · Biomolecules · doi:10.3390/biom9030096 · Cited by 53 · see citing works
Marroquí, L., Martínez‐Pinna, J., Castellano-Muñoz, M., dos Santos, R. S., Medina-Gali, R. M., Soriano, S., Quesada, I., Gustafsson, J.-Α., Encinar, J. A., & Nadal, Á. (2020) · Chemosphere · doi:10.1016/j.chemosphere.2020.129051 · Cited by 49 · see citing works
Self-citationBile acid metabolism in health and ageing-related diseases
Li, X., Fang, C., Zhao, R., Zou, L., Miao, H., & Zhao, Y. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116313 · Cited by 49 · see citing works
Liu, R., Wang, J., Zhao, Y.-K., Qi, Z., Yang, X., Gao, Y., Qin, L., Bai, M., Liu, J., Liang, Y., et al. (2024) · Phytomedicine · doi:10.1016/j.phymed.2023.155329 · Cited by 46 · see citing works
Zangerolamo, L., Carvalho, M. U. W. B. D., & Barbosa, H. C. L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26146547 · Cited by 47 · see citing works
Regulation of glucose and lipid metabolism by the pancreatic and extra-pancreatic actions of taurine
Ribeiro, R. A., Bonfleur, M. L., Batista, T. M., Borck, P. C., & Carneiro, E. M. (2018) · Amino Acids · doi:10.1007/s00726-018-2650-3 · Cited by 43 · see citing works
Self-citationUpdate on the development of TGR5 agonists for human diseases
Jin, W., Zheng, M., Chen, Y., & Xiong, H. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116462 · Cited by 41 · see citing works
García-Gutiérrez, E., O’Mahony, A. K., dos Santos, R. S., Marroquí, L., & Cotter, P. D. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2401654 · Cited by 42 · see citing works
Insights by which TUDCA is a potential therapy against adiposity
Freitas, I. N., junior, J. A. D. S., de Oliveira, K. M., Alves, B. L., Araújo, T. R., Camporez, J. P., Carneiro, E. M., & Davel, A. P. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1090039 · Cited by 38 · see citing works
Self-citationSong, M., Zhang, F., Fu, Y., Yi, X., Feng, S., Liu, Z., Deng, D., Yang, Q., Yu, M., Zhu, C., et al. (2022) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-022-00713-3 · Cited by 37 · see citing works
Kurauti, M. A., Dias, R. D. F., Ferreira, S. M., Vettorazzi, J. F., Nardelli, T. R., Araújo, H. N., dos Santos, G. J., Carneiro, E. M., Boschero, A. C., de Rezende, L. F., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0160239 · Cited by 36 · see citing works
Self-citationWang, H., Guo, Y. Z., Han, W., Liang, M., Xiao, X., Jiang, X., & Yu, W. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c04630 · Cited by 38 · see citing works
Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis
Ahn, T., Kim, K., Joshi, H. P., Park, K. H., Kyung, J. W., Choi, U. Y., Sohn, S., Sheen, S. H., Shin, D.-E., Lee, S., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124274 · Cited by 33 · see citing works
Wu, H., Yu, N., Wang, X., Yang, Y., & Liang, H. (2020) · Biological Research · doi:10.1186/s40659-020-00323-1 · Cited by 32 · see citing works
TGR5 agonists for diabetes treatment: a patent review and clinical advancements (2012-present)
Bhimanwar, R. S., & Mittal, A. (2021) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2022.1994551 · Cited by 29 · see citing works
Development of betulinic acid as an agonist of TGR5 receptor using a new in vitro assay
Cheng, J., Cheng, K., Li, Y., Lo, S., Chang, C.-H., & Lee, K. (2016) · Drug Design Development and Therapy · doi:10.2147/dddt.s113197 · Cited by 29 · see citing works
Atanes, P., Ashik, T., & Persaud, S. J. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107928 · Cited by 28 · see citing works
Bile Acids and Microbiota Interplay in Pancreatic Cancer
Malhotra, P., Palanisamy, R., Caparros-Martin, J. A., & Falasca, M. (2023) · Cancers · doi:10.3390/cancers15143573 · Cited by 26 · see citing works
Zhang, M., Xiao, B., Chen, X., Ou, B., & Wang, S. (2023) · Acta Physiologica · doi:10.1111/apha.14065 · Cited by 26 · see citing works
Eukaryotic cell survival mechanisms: Disease relevance and therapeutic intervention
Twayana, K. S., & Ravanan, P. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.05.002 · Cited by 25 · see citing works
Liu, M., Ren, L., Zhong, X., Ding, Y., Liu, T., Liu, Z., Yang, X., Cui, L., Yang, L., Fan, Y., et al. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00152 · Cited by 24 · see citing works
The bile acid TUDCA reduces age-related hyperinsulinemia in mice
Zangerolamo, L., Carvalho, M. U. W. B. D., Barssotti, L., Soares, G. M., Marmentini, C., Boschero, A. C., & Barbosa, H. C. L. (2022) · Scientific Reports · doi:10.1038/s41598-022-26915-3 · Cited by 25 · see citing works
Self-citationAraújo, T. R., Muniz, M. R. R., Alves, B. L., dos Santos, L. M. B., Bonfim, M. F., junior, J. A. D. S., Vettorazzi, J. F., Zoppi, C. C., & Carneiro, E. M. (2022) · Food Research International · doi:10.1016/j.foodres.2022.111331 · Cited by 23 · see citing works
Self-citationChen, S., Hao, X., Yu, L., Zhang, P., Cao, W., Chen, H., & Zhu, D. (2017) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2017.1369118 · Cited by 23 · see citing works
Mooranian, A., Zamani, N., Ionescu, C. M., Takechi, R., Luna, G., Mikov, M., Goločorbin-Kon, S., Kovačević, B., & Al‐Salami, H. (2020) · Pharmacological Reports · doi:10.1007/s43440-019-00030-z · Cited by 23 · see citing works
Emerging Anti-Diabetic Drugs for Beta-Cell Protection in Type 1 Diabetes
Ajmal, N., Bogart, M. C., Khan, P., Max-Harry, I. M., & Nunemaker, C. S. (2023) · Cells · doi:10.3390/cells12111472 · Cited by 20 · see citing works
Maternal glucose homeostasis is impaired in mouse models of gestational cholestasis
Bellafante, E., McIlvride, S., Nikolova, V., Fan, H. M., Manna, L. B., Chambers, J., Machirori, M., Banerjee, A., Murphy, K. G., Martineau, M., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-67968-6 · Cited by 20 · see citing works
GPCR-mediated effects of fatty acids and bile acids on glucose homeostasis
Oteng, A., & Liu, L. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1206063 · Cited by 19 · see citing works
Xue, C., Jia, H., Cao, R., Cai, W., Hong, W., Tu, J., Wang, S., Jiang, Q., Bi, C., Shan, A., et al. (2024) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-024-01037-0 · Cited by 20 · see citing works
Chen, P., Jiang, X., Fu, J., Ou, C., Li, Y., Jia, J., & Liao, C. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1419160 · Cited by 19 · see citing works
Kårhus, M. L., Brønden, A., Sonne, D. P., Vilsbøll, T., & Knop, F. K. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12946 · Cited by 19 · see citing works
da Silva, J. A., Figueiredo, L. S., Chaves, J. D. O., de Oliveira, K. M., Carneiro, E. M., Abreu, P. A., & Ribeiro, R. A. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.120020 · Cited by 18 · see citing works
Self-citationKim, B., Arai, Y., Park, E., Park, S., Bello, A. B., Han, I., & Lee, S. (2017) · Tissue Engineering Part A · doi:10.1089/ten.tea.2016.0349 · Cited by 17 · see citing works
Regulation of Adipsin Expression by Endoplasmic Reticulum Stress in Adipocytes
Ryu, K., Jeon, E. J., Leem, J., Park, J., & Cho, H. (2020) · Biomolecules · doi:10.3390/biom10020314 · Cited by 17 · see citing works
Zhang, X., Yan, Y., Zhang, F., Zhang, X., Xu, H., Liu, Y., & Huang, Y. (2023) · Journal of Functional Foods · doi:10.1016/j.jff.2023.105496 · Cited by 16 · see citing works
TUDCA receptors and their role on pancreatic beta cells
Rosa, L. R. D. O., Vettorazzi, J. F., Zangerolamo, L., Carneiro, E. M., & Barbosa, H. C. L. (2021) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2021.09.003 · Cited by 15 · see citing works
Self-citationTanaka, C., Harada, N., Teraoka, Y., Urushizaki, H., Shinmori, Y., Onishi, T., Yotsumoto, Y., Ito, Y., Kitakaze, T., Inui, T., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-53380-x · Cited by 15 · see citing works
Tao, Z.-S., Li, T., Wu, X.-J., & Yang, M. (2021) · Journal of Biomaterials Applications · doi:10.1177/08853282211027678 · Cited by 14 · see citing works
Li, W., Gong, Y., Liu, N., Chen, S., Yue, M., Li, J., Huang, X., Chen, N., & Li, S. (2024) · Aquaculture · doi:10.1016/j.aquaculture.2024.740745 · Cited by 13 · see citing works
Wang, Q., Li, W., Zhang, X., Chung, S. L., Dai, J., & Jin, Z. (2023) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.2518 · Cited by 13 · see citing works
Ji, Y., Gu, Y., Liu, H., Yang, Z., & Li, C. (2016) · Fisheries Science · doi:10.1007/s12562-016-1032-6 · Cited by 13 · see citing works
Zhang, C., Gao, Y., Huang, Y., Qin, Y., Li, Y., Chen, Q., Wu, T., Zhang, Y., Zhang, Y., Deng, D., et al. (2025) · mSystems · doi:10.1128/msystems.00965-25 · Cited by 11 · see citing works
Indumathi, B., Oruganti, S. S., Sreenu, B., & Kutala, V. K. (2020) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-020-00932-3 · Cited by 11 · see citing works
Exploring the impact of type 2 diabetes and glucose-lowering drugs on gut microbiome dynamics
Tariq, H. M. A., Khan, N. Y., Manzoor, H., & Kayani, M. U. R. (2025) · Discover Medicine · doi:10.1007/s44337-025-00241-9 · Cited by 12 · see citing works
O’Kell, A. L., Wasserfall, C. H., Guingab-Cagmat, J. D., Webb-Roberston, B.-J. M., Atkinson, M. A., & Garrett, T. J. (2021) · Metabolomics · doi:10.1007/s11306-021-01850-y · Cited by 9 · see citing works
Lee, C., Chu, C., Tsai, H.-J., Ke, L., Lee, H., Yeh, J., Chen, C., & Wu, B. (2017) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2017.11.017 · Cited by 9 · see citing works
Bile Acids and Type 2 Diabetes: Roles in Glucose Homeostasis and Therapeutic Opportunities
Lin, Y., Hu, C., Wang, S., & Lin, H. (2025) · Metabolites · doi:10.3390/metabo15060401 · Cited by 8 · see citing works
Mendes, C. P., Postal, B. G., Oliveira, G. C., Castro, A. J. G., Frederico, M. J., Moraes, A. P., Neuenfeldt, P., Nunes, R., Menegaz, D., & Silva, F. R. M. B. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26746 · Cited by 7 · see citing works
Mustapha, S., Azemi, A. K., Ahmad, W. A. N. W., Rasool, A. H. G., Mustafa, M. R., & Mokhtar, S. S. (2022) · Molecules · doi:10.3390/molecules27165107 · Cited by 7 · see citing works
Improving stem cell-derived pancreatic islets using single-cell multiome-inferred regulomes
Zhu, H., Wang, G., Nguyen-Ngoc, K.-V., Kim, D., Miller, M., Goss, G., Kovsky, J., Harrington, A. R., Saunders, D., Melton, R., et al. (2022) · doi:10.1101/2022.09.25.509355 · Cited by 85 · see citing works
Sun, J., Wu, Z., Li, J., Shang, L., Zhao, Y., & Li, L. (2025) · Research · doi:10.34133/research.0923 · Cited by 6 · see citing works
Comparative effects of sex hormone deprivation on the brain of insulin-resistant rats
Sripetchwandee, J., Pintana, H., Sa‐nguanmoo, P., Boonnag, C., Pratchayasakul, W., Chattipakorn, N., & Chattipakorn, S. C. (2019) · Journal of Endocrinology · doi:10.1530/joe-18-0552 · Cited by 6 · see citing works
Bile acid signaling, metabolism, and aging
Sun, J., Zhang, S., Jin, L., & Huang, W. (2026) · Liver Research · doi:10.1016/j.livres.2026.02.002 · Cited by 7 · see citing works
Bile acids: New regulators of the cardiometabolic crosstalk
Wolf, S., Nagler, M., & Osto, E. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108320 · Cited by 4 · see citing works
Mechanism-driven multitarget therapeutics for diabetic peripheral neuropathy
Kong, S., Nan, G., Wang, Y., Du, M., Kong, Y., Zhu, L., Shen, X., Li, X., & Dong, C. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.10.053 · Cited by 4 · see citing works
High-concentrate diet decreases lamb fatty acid contents by regulating bile acid composition
Zheng, K., Guo, L., Cao, Y., Yin, Y., Gao, H., Zhang, X., Jiang, J., Li, J., Huang, X., Li, K., et al. (2024) · Food Chemistry X · doi:10.1016/j.fochx.2024.101871 · Cited by 3 · see citing works
da Silva, J. A., Vettorazzi, J. F., Soriano, S., Bru-Tarí, E., Boronat‐Belda, T., Castellano-Muñoz, M., Borck, P. C., Ribeiro, R. A., Soares, G. M., Lubaczeuski, C., et al. (2025) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2025.110076 · Cited by 3 · see citing works
Self-citationCao, M., Qiao, F.-X., Wang, Q., Luo, J., Ju, Y., Wang, X., & Chen, X. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117377 · Cited by 3 · see citing works
Simões, B. E. S., Muniz, M. R. R., ARAUJO, T., Carneiro, E. M., & Simionato, A. V. C. (2024) · Electrophoresis · doi:10.1002/elps.202300223 · Cited by 3 · see citing works
Self-citationTauroursodeoxycholic acid (TUDCA) ameliorates age‐related skeletal muscle loss
Carvalho, M. U. W. B. D., Barssotti, L., dos Santos, L. M. B., Rosa, L. R. D. O., Gomes‐Marcondes, M. C. C., CARNEIRO, E. M., Barbosa, H. C. L., & Zangerolamo, L. (2026) · The Journal of Physiology · doi:10.1113/jp290683 · Cited by 2 · see citing works
Self-citationAraújo, T. R., Santiago, D., Simões, P., Guimarães, F., Zoppi, C. C., & Carneiro, E. M. (2022) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-93337-1_28 · Cited by 2 · see citing works
Self-citationLiu, K., Ren, Y., Liu, Y., & Zhang, Y. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.121304 · Cited by 1 · see citing works
Gastric Bypass Surgery Regulates Glucose Homeostasis Through the Hypothalamus
Quan, H. (2019) · Clinical Medicine Research · doi:10.11648/j.cmr.20190802.11 · Cited by 1 · see citing works
Editorial: Pharmacological and non-pharmacological therapy for obesity and diabetes - volume II
Oliveira, A. G., Carvalho, B. M., & Rocha, G. Z. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1252536 · Cited by 1 · see citing works
Figueiredo, M. S., Vettorazzi, J. F., Branco, R. C. S., & Carneiro, E. M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816093-0.00011-2
Self-citationCorrelation between Intestinal Flora-Bile Acid Related Pathway and Type 2 Diabetes
岳, 晓. (2023) · Advances in Clinical Medicine · doi:10.12677/acm.2023.13122796
Impacts of dietary fat on multi tissue gene expression in the desert-adapted cactus mouse
Blumstein, D. M., & MacManes, M. D. (2024) · Journal of Experimental Biology · doi:10.1242/jeb.247978
Wu, H., Yu, N., Wang, X., Yang, Y., & Liang, H. (2020) · Figshare · doi:10.6084/m9.figshare.13316902
- Authors
- Vettorazzi, J. F., Ribeiro, R. A., Borck, P. C., Branco, R. C. S., Soriano, S., Merino, B., Boschero, A. C., Nadal, A., Quesada, I., & Carneiro, E. M.
- Affiliations
- Universitat de Miguel Hernández d'Elx (ES)
- Universidade Federal do Rio de Janeiro (BR)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- University of Alicante (ES)
- Corresponding author
- Carneiro, Everardo Magalhães
- ORCID
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 65
- Issue
- 3
- Pages
- 54-63
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2186068515
- Cited by
- 104
- References
- 38
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 14 · 2023: 13 · 2022: 9 · 2021: 10 · 2020: 13 · 2019: 10 · 2018: 7 · 2017: 8 · 2016: 5
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- Repositorio Institucional de la Universidad de Alicante (Universidad de Alicante) (submittedVersion)
- Funders
- Fundacão de Amparo á Pesquisa do Estado de São Paulo (FAPESP 2013/01318-4)
- Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq 200030/2014-0)
- Instituto Nacional de Obesidade e Diabetes (CNPq/FAPESP)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
- Spanish Ministerio de Ciencia e Innovación (BFU2013-42789-P, BFU2011-28358)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Keywords
- tauroursodeoxycholic acid, bile acids, glucose-stimulated insulin secretion, pancreatic beta cells, cAMP/PKA signaling, TGR5, G protein-coupled receptors, CREB phosphorylation, pancreatic islets, insulin secretion
- MeSH terms
- Cyclic AMP, Animals, Dose-Response Relationship, Drug, Glucose, Insulin, Male, Mice, Inbred C57BL, Phosphorylation, Taurochenodeoxycholic Acid, Signal Transduction, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinases, Calcium Signaling, Receptors, G-Protein-Coupled, Protein Kinase Inhibitors, Insulin-Secreting Cells, Mice, KATP Channels, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
