Anti-inflammatory action of exendin-4 in human islets is enhanced by phosphodiesterase inhibitors: potential therapeutic benefits in diabetic patients
Open accessAbstract
Aims/hypothesis Exendin-4, a glucagon-like peptide-1 (GLP-1) analogue, is reported to have modest anti-inflammatory effects in addition to that of improving beta cell survival. We therefore sought to determine whether exendin-4 decreases expression of the gene encoding chemokine (C-X-C motif) ligand (CXCL)10, which plays a role in initiating insulitis in type 1 diabetes. Methods The expression of CXCL10 in human islets was determined at the mRNA level by real-time RT-PCR analysis and at the protein level by western blotting. The level of CXCL10 in culture medium was measured by ELISA. Pathway-specific gene expression profiling was carried out to determine the expression of a panel of genes encoding chemokines and cytokines in human islets exposed to cytokines. Results IFN-γ induced expression of CXCL10 through activation of signal transducer and activator of transcription-1 (STAT-1). A combination of cytokines (IL-1β, TNF-α and IFN-γ) showed strong synergy in the induction of numerous chemokines and cytokines through nuclear factor kappa B and STAT-1. Exendin-4 suppressed basal expression of several inflammatory mediators. In combination with phosphodiesterase inhibitors, exendin-4 also decreased IFN-γ-induced CXCL10 expression in human islets and in MIN6 cells (a mouse beta cell line), and its secretion into the culture medium. Exendin-4 action was mimicked by forskolin, an activator of adenylyl cyclase, and by dibutyryl cyclic AMP. Protein kinase A was not involved in mediating exendin-4 action on CXCL10. The mechanism of exendin-4's anti-inflammatory action involved decreases in STAT-1 levels. Conclusions/interpretation These findings suggest that the GLP-1-cyclic AMP pathway decreases islet inflammation in addition to its known effects on beta cell survival.
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?
Exendin-4 (100 nM) decreased IFN-γ-induced STAT1, which is important for CXCL10 expression in the pancreatic beta-cell line, MIN6 cells, and human islets.
“Exendin-4 (100 nM) decreased IFN-γ-induced signal transducer and activator of transcription-1 (STAT1), which is important for CXCL10 expression in the pancreatic beta-cell line, MIN6 cells, and human islets.”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [48]
Suppression of CXCL10 production by exendin-4 could reduce islet inflammation by decreasing cytotoxic T lymphocyte recruitment into the islets in autoimmune type 1 diabetes.
“Therefore, suppression of CXCL10 production by exendin-4 could reduce islet inflammation by decreasing cytotoxic T lymphocyte recruitment into the islets in autoimmune type 1 diabetes [48].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [48]
Cites
Chemokines — Chemotactic Cytokines That Mediate Inflammation
Luster, A. D. (1998) · New England Journal of Medicine · doi:10.1056/nejm199802123380706 · Cited by 3,634 · see citing works
The biology of incretin hormones
Drucker, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.004 · Cited by 2,210 · see citing works
Miyazaki, J., Araki, K., Yamato, E., Ikegami, H., Asano, T., Shibasaki, Y., Oka, Y., & Yamamura, K. (1990) · Endocrinology · doi:10.1210/endo-127-1-126 · Cited by 1,267 · see citing works
The role of inflammation in insulitis and β-cell loss in type 1 diabetes
Eizirik, D. L., Colli, M. L., & Ortis, F. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.21 · Cited by 1,011 · see citing works
Overview of PDEs and Their Regulation
Omori, K., & Kotera, J. (2007) · Circulation Research · doi:10.1161/01.res.0000256354.95791.f1 · Cited by 797 · see citing works
Increased Number of Islet-Associated Macrophages in Type 2 Diabetes
Ehses, J. A., Perren, A. A., Eppler, E., Ribaux, P., Pospisilik, J. A., Maor-Cahn, R., Guéripel, X., Ellingsgaard, H., Schneider, M. K. J., Biollaz, G., et al. (2007) · Diabetes · doi:10.2337/db06-1650 · Cited by 783 · see citing works
Chemokines in pathology and medicine
Baggiolini, M. (2001) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.2001.00867.x · Cited by 710 · see citing works
Biochemical characterization of a gamma interferon-inducible cytokine (IP-10)
Luster, A., & Ravetch, J. (1987) · Journal of Experimental Medicine · doi:10.1084/jem.166.4.1084 · Cited by 676 · see citing works
Schweppe, R. E., Klopper, J. P., Korch, C., Pugazhenthi, U., Benezra, M., Knauf, J. A., Fagin, J. A., Marlow, L. A., Copland, J. A., Smallridge, R. C., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1102 · Cited by 563 · see citing works
Self-citationInflammatory mediators and islet ?-cell failure: a link between type 1 and type 2 diabetes
Donath, M. Y., St�rling, J., Maedler, K., & Mandrup-Poulsen, T. (2003) · Journal of Molecular Medicine · doi:10.1007/s00109-003-0450-y · Cited by 422 · see citing works
Neville, L. F., Mathiak, G., & Bagasra, O. (1997) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(97)00015-4 · Cited by 352 · see citing works
Islet Inflammation in Type 2 Diabetes
Donath, M. Y., Schumann, D., Faulenbach, M. V., Ellingsgaard, H., Perren, A. A., & Ehses, J. A. (2008) · Diabetes Care · doi:10.2337/dc08-s243 · Cited by 334 · see citing works
β cells are responsible for CXCR3-mediated T-cell infiltration in insulitis
Frigerio, S., Junt, T., Lu, B., Gerard, C. J., Zumsteg, U., Holländer, G. A., & Piali, L. (2002) · Nature Medicine · doi:10.1038/nm1202-792 · Cited by 302 · see citing works
Kim, S., Moon, M., & Park, S. (2009) · Journal of Endocrinology · doi:10.1677/joe-09-0132 · Cited by 263 · see citing works
Aronoff, D. M., Canetti, C. D. A., Serezani, C. H., Luo, M., & Peters-Golden, M. L. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.2.595 · Cited by 241 · see citing works
CXCL10 Impairs β Cell Function and Viability in Diabetes through TLR4 Signaling
Schulthess, F. T., Paroni, F., Sauter, N. S., Shu, L., Ribaux, P., Haataja, L., Strieter, R. M., Oberholzer, J., King, C. C., & Maedler, K. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.01.003 · Cited by 209 · see citing works
Glucagon-like peptide-1 inhibits LPS-induced IL-1β production in cultured rat astrocytes
Iwai, T., Ito, S., Tanimitsu, K., Udagawa, S., & Oka, J.-I. (2006) · Neuroscience Research · doi:10.1016/j.neures.2006.04.008 · Cited by 207 · see citing works
Cardozo, A. K., Proost, P., Gysemans, C. A., Chen, M., Mathieu, C., & Eizirik, D. L. (2003) · Diabetologia · doi:10.1007/s00125-002-1017-0 · Cited by 197 · see citing works
Islet inflammation and CXCL10 in recent-onset type 1 diabetes
Roep, B. O., Kleijwegt, F. S., van Halteren, A. G. S., Bonato, V., Boggi, U., Vendrame, F., Marchetti, P., & Dotta, F. (2010) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2009.04087.x · Cited by 186 · see citing works
Majumder, S., Zhou, L. Z.-H., Chaturvedi, P., Babcock, G., Aras, S., & Ransohoff, R. M. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.9.4736 · Cited by 181 · see citing works
Christen, U., McGavern, D. B., Luster, A. D., von Herrath, M. G., & Oldstone, M. B. A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.12.6838 · Cited by 179 · see citing works
Mechanisms of Coxsackievirus-Induced Damage to Human Pancreaticβ -Cells1
Roivainen, M., Rasilainen, S. K., Ylipaasto, P., Nissinen, R., Ustinov, J., Bouwens, L., Eizirik, D. L., Hovi, T., & Otonkoski, T. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.1.6306 · Cited by 173 · see citing works
Majumder, S., Zhou, L., Chaturvedi, P., Babcock, G., Aras, S., & Ransohoff, R. M. (1998) · PubMed · Cited by 171 · see citing works
Sherry, N. A., Chen, W., Kushner, J. A., Glandt, M., Tang, Q., Tsai, S., Santamaria, P., Bluestone, J. A., Brillantes, A.-M. B., & Herold, K. C. (2007) · Endocrinology · doi:10.1210/en.2007-0358 · Cited by 169 · see citing works
Nicoletti, F., Conget, I., Mauro, M. D., Marco, R. D., Mazzarino, M., Bendtzen, K., Messina, A. A., & Gomis, R. (2002) · Diabetologia · doi:10.1007/s00125-002-0879-5 · Cited by 168 · see citing works
Enterovirus Infection, CXC Chemokine Ligand 10 (CXCL10), and CXCR3 Circuit
Tanaka, S. A., Nishida, Y., Aida, K., Maruyama, T., Shimada, A., Suzuki, M., Shimura, H., Takizawa, S., Takahashi, M., Akiyama, D., et al. (2009) · Diabetes · doi:10.2337/db09-0091 · Cited by 164 · see citing works
Cure of Overt Diabetes in NOD Mice by Transient Treatment With Anti-Lymphocyte Serum and Exendin-4
Ogawa, N., List, J. F., Habener, J. F., & Maki, T. (2004) · Diabetes · doi:10.2337/diabetes.53.7.1700 · Cited by 156 · see citing works
Jun, H., & Yoon, J. W. (2001) · Diabetologia · doi:10.1007/s001250051614 · Cited by 149 · see citing works
Inhibition of cytokines and JAK-STAT activation by distinct signaling pathways.
Sengupta, T. K., Schmitt, E. M., & Ivashkiv, L. B. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.18.9499 · Cited by 132 · see citing works
Exendin-4 modulates diabetes onset in nonobese diabetic mice
Hadjiyanni, I., Baggio, L. L., Poussier, P., & Drucker, D. J. (2008) · Endocrinology · doi:10.1210/en.2007-1137 · Cited by 110 · see citing works
Yeruva, S., Ramadori, G. P., & Raddatz, D. (2007) · International Journal of Colorectal Disease · doi:10.1007/s00384-007-0396-6 · Cited by 108 · see citing works
Kim, S., Nian, C., Doudet, D. J., & McIntosh, C. H. S. (2008) · Diabetes · doi:10.2337/db08-1101 · Cited by 106 · see citing works
Sarkar, S. A., Kutlu, B., Velmurugan, K., Kizaka‐Kondoh, S., Lee, C. E., Wong, R., Valentine, A., Davidson, H. W., Hutton, J. C., & Pugazhenthi, S. (2009) · Diabetologia · doi:10.1007/s00125-009-1331-x · Cited by 96 · see citing works
Self-citationZhang, J., Tokui, Y., Yamagata, K., Kozawa, J., Sayama, K., Iwahashi, H., Okita, K., Miuchi, M., Konya, H., Hamaguchi, T., et al. (2007) · Diabetologia · doi:10.1007/s00125-007-0737-6 · Cited by 79 · see citing works
Morimoto, J., Yoneyama, H., Shimada, A., Shigihara, T., Yamada, S., Oikawa, Y., Matsushima, K., Saruta, T., & Narumi, S. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.11.7017 · Cited by 73 · see citing works
Liu, D., Cardozo, A. K., Darville, M. I., & Eizirik, D. L. (2002) · Endocrinology · doi:10.1210/endo.143.4.8737 · Cited by 72 · see citing works
IP-10 and Type 1 Diabetes: A Question of Time and Location
Christen, U., & von Herrath, M. G. (2004) · Autoimmunity · doi:10.1080/08916930410001713124 · Cited by 70 · see citing works
von Herrath, M., & Holz, A. (1997) · Journal of Autoimmunity · doi:10.1006/jaut.1997.0131 · Cited by 70 · see citing works
The phosphodiesterase inhibitors pentoxifylline and rolipram prevent diabetes in NOD mice.
Liang, L., Beshay, E., & Prud’homme, G. J. (1998) · Diabetes · doi:10.2337/diabetes.47.4.570 · Cited by 69 · see citing works
Parker, J. C., VanVolkenburg, M. A., Ketchum, R. J., Brayman, K. L., & Andrews, K. M. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2858 · Cited by 57 · see citing works
Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes
Yang, Z., Chen, M., Carter, J. D., Nunemaker, C. S., Garmey, J. C., Kimble, S. D., & Nadler, J. L. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.03.177 · Cited by 50 · see citing works
Stošić‐Grujičić, S., Maksimović‐Ivanić, D., Badovinac, V. P., Samardžić, T., Trajković, V., Lukić, M. L., & Stojković, M. M. (2001) · Journal of Autoimmunity · doi:10.1006/jaut.2000.0456 · Cited by 46 · see citing works
Chemokines in islet allograft rejection
Abdi, R., Means, T. K., & Luster, A. D. (2003) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.362 · Cited by 41 · see citing works
Sarkar, S., Gunter, J., Bouchard, R. J., Reusch, J., Wiseman, A., Gill, R. G., Hutton, J., & Pugazhenthi, S. (2007) · Diabetologia · doi:10.1007/s00125-007-0707-z · Cited by 39 · see citing works
Self-citationBerg, A. ‐., Korsgren, O., & Frisk, G. (2006) · Diabetologia · doi:10.1007/s00125-006-0429-7 · Cited by 38 · see citing works
Regulation by cAMP of STAT1 Activation in Hepatic Stellate Cells
Kawada, N., Uoya, M., Seki, S., Kuroki, T., & Kobayashi, K. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6481 · Cited by 33 · see citing works
Pentoxifylline in the treatment of children with new-onset type I diabetes mellitus.
MacDonald, M. J., Shahidi, N. T., Allen, D. B., Lustig, R. H., Mitchell, T. L., & Cornwell, S. T. (1994) · PubMed · Cited by 22 · see citing works
Exenatide blocks JAK1-STAT1 in pancreatic beta cells
Couto, F. M., Minn, A. H., Pise-Masison, C. A., Radonovich, M., Brady, J. N., Hanson, M. S., Fernandez, L. A., Wang, P., Kendziorski, C. M., & Shalev, A. (2007) · Metabolism · doi:10.1016/j.metabol.2007.02.004 · Cited by 21 · see citing works
Pentoxifylline in the Treatment of Children With New-Onset Type I Diabetes Mellitus
MacDonald, M. J. (1994) · JAMA · doi:10.1001/jama.1994.03510250043028 · Cited by 11 · see citing works
Theophylline protects against diabetes in BB rats and potentiates cyclosporine protection
Rabinovitch, A., & SUMOSKI, W. (1990) · Diabetologia · doi:10.1007/bf00405114 · Cited by 10 · see citing works
New Therapeutic Horizons: Mapping the Future of Glycemic Control With Incretin-based Therapy
Campbell, R. K., & Miller, S. (2009) · The Science of Diabetes Self-Management and Care · doi:10.1177/0145721709342900 · Cited by 8 · see citing works
Inhibition of pro-inflammatory cytokine receptor signalling by cAMP in vascular endothelial cells
Sands, W. A., & Palmer, T. M. (2005) · Biochemical Society Transactions · doi:10.1042/bst0331126 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Targeting inflammation in the treatment of type 2 diabetes: time to start
Donath, M. Y. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4275 · Cited by 690 · see citing works
Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control
Lee, Y.-S., & Jun, H.-S. (2016) · Mediators of Inflammation · doi:10.1155/2016/3094642 · Cited by 503 · see citing works
Anti-diabetic actions of glucagon-like peptide-1 on pancreatic beta-cells
Lee, Y.-S., & Jun, H.-S. (2014) · Metabolism · doi:10.1016/j.metabol.2013.09.010 · Cited by 315 · see citing works
The expanding incretin universe: from basic biology to clinical translation
Drucker, D. J., & Holst, J. J. (2023) · Diabetologia · doi:10.1007/s00125-023-05906-7 · Cited by 243 · see citing works
The DPP-4 Inhibitor Linagliptin Counteracts Stroke in the Normal and Diabetic Mouse Brain
Darsalia, V., Ortsäter, H., Olverling, A., Darlöf, E., Wolbert, P., Nyström, T., Klein, T., Sjöholm, Å., & Patrone, C. (2012) · Diabetes · doi:10.2337/db12-0988 · Cited by 147 · see citing works
Expression and Regulation of Chemokines in Murine and Human Type 1 Diabetes
Sarkar, S. A., Lee, C. E., Victorino, F., Nguyen, T. T., Walters, J. A., Burrack, A., Eberlein, J., Hildemann, S. K., & Homann, D. (2011) · Diabetes · doi:10.2337/db11-0853 · Cited by 139 · see citing works
Saxagliptin: A novel antiparkinsonian approach
Nassar, N. N., Al‐Shorbagy, M. Y., Arab, H. H., & Abdallah, D. M. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.10.007 · Cited by 122 · see citing works
CXCR3, CXCL10 and type 1 diabetes
Antonelli, A., Ferrari, S. M., Corrado, A., Ferrannini, E., & Fallahi, P. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.01.006 · Cited by 116 · see citing works
Wang, X.-C. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i40.14821 · Cited by 109 · see citing works
Wu, H., Tang, X.-Q., Mao, X.-F., & Wang, Y. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1799-17.2017 · Cited by 87 · see citing works
Portha, B., Tourrel-Cuzin, C., & Movassat, J. (2011) · Experimental Diabetes Research · doi:10.1155/2011/376509 · Cited by 85 · see citing works
Pugazhenthi, S., Zhang, Y., Bouchard, R. J., & Mahaffey, G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069585 · Cited by 85 · see citing works
Self-citationGLP-1 nanomedicine alleviates gut inflammation
Anbazhagan, A. N., Thaqi, M., Priyamvada, S., Jayawardena, D., Kumar, A., Gujral, T., Chatterjee, I., Mugarza, E., Saksena, S., Onyuksel, H., et al. (2017) · Nanomedicine: Nanotechnology, Biology and Medicine · doi:10.1016/j.nano.2016.08.004 · Cited by 80 · see citing works
He, L., Wong, C. K., Cheung, K. K., Yau, H. C., Fu, A., Zhao, H., Leung, K. M., Kong, A. P., Wong, G. W., Chan, P. K., et al. (2013) · Journal of Diabetes Investigation · doi:10.1111/jdi.12063 · Cited by 70 · see citing works
Dalvi, P. S., Nazarians-Armavil, A., Purser, M. J., & Belsham, D. D. (2012) · Endocrinology · doi:10.1210/en.2011-1795 · Cited by 69 · see citing works
Anti-Inflammatory Properties of Exenatide in Human Pancreatic Islets
Cechin, S. R., Pérez-Álvarez, I., Fenjves, E., Molano, R. D., Pileggi, A., Berggren, P.-O., Ricordi, C., & Pastori, R. L. (2012) · Cell Transplantation · doi:10.3727/096368911x576027 · Cited by 67 · see citing works
Robinson, E., Cassidy, R. S., Tate, M., Zhao, Y., Lockhart, S. M., Calderwood, D., Church, R. H., McGahon, M. K., Brazil, D. P., McDermott, B. J., et al. (2015) · Basic Research in Cardiology · doi:10.1007/s00395-015-0476-7 · Cited by 67 · see citing works
GLP ‐1 analogue prevents NAFLD in ApoE KO mice with diet and Acrp30 knockdown by inhibiting c‐ JNK
Zhang, L., Yang, M., Ren, H., Hu, H., Boden, G. H., Li, L., & Yang, G. (2013) · Liver International · doi:10.1111/liv.12120 · Cited by 65 · see citing works
Anti-inflammatory potentials of incretin-based therapies used in the management of diabetes
Yaribeygi, H., Maleki, M., Sathyapalan, T., Jamialahmadi, T., & Sahebkar, A. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.117152 · Cited by 64 · see citing works
van Raalte, D. H., & Verchere, C. B. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12935 · Cited by 61 · see citing works
Antiapoptotic Actions of Exendin-4 against Hypoxia and Cytokines Are Augmented by CREB
Velmurugan, K., Balamurugan, A. N., Loganathan, G., Ahmad, A., Hering, B. J., & Pugazhenthi, S. (2012) · Endocrinology · doi:10.1210/en.2011-1895 · Cited by 53 · see citing works
Self-citationCho, J. M., Jang, H. W., Cheon, H., Jeong, Y. T., Kim, D., Lim, Y.-M., Choi, S., Yang, E.-K., Shin, C.-Y., Son, M. H., et al. (2010) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2010.10.012 · Cited by 51 · see citing works
Wu, S., Gao, L., Cipriani, A., Huang, Y., Yang, Z., Yang, J., Yu, S., Zhang, Y., Chai, S., Zhang, Z., et al. (2018) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13613 · Cited by 47 · see citing works
Neuroprotective actions of Glucagon‐like peptide‐1 in differentiated human neuroprogenitor cells
Velmurugan, K., Bouchard, R. J., Mahaffey, G., & Pugazhenthi, S. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12036 · Cited by 42 · see citing works
Self-citationKnudsen, S. H., & Pedersen, B. K. (2015) · Current Diabetes Reports · doi:10.1007/s11892-015-0642-1 · Cited by 41 · see citing works
Luo, Y., Yang, P., Li, Z., Luo, Y., Shen, J., Li, R., Zheng, H., Liang, Y., & Xia, N. (2019) · Drug Design Development and Therapy · doi:10.2147/dddt.s224688 · Cited by 41 · see citing works
Endogenous GLP-1 as a key self-defense molecule against lipotoxicity in pancreatic islets
HUANG, C., YUAN, L., & CAO, S. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2207 · Cited by 41 · see citing works
Nanotechnology in the Treatment of Inflammatory Bowel Disease
Giron, F., Pastò, A., Tasciotti, E., & Abraham, B. P. (2019) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izz205 · Cited by 40 · see citing works
Exendin-4 upregulates the expression of Wnt-4, a novel regulator of pancreatic β-cell proliferation
Heller, C., Kühn, M. C., Mülders-Opgenoorth, B., Schott, M., Willenberg, H. S., Scherbaum, W. A., & Schinner, S. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00144.2011 · Cited by 32 · see citing works
Nakamura, T., Ito, T., Uchida, M., Hijioka, M., Igarashi, H., Oono, T., Kato, M., Nakamura, K., Suzuki, K., Jensen, R. T., et al. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.133 · Cited by 30 · see citing works
Bakbak, E., Terenzi, D. C., Trac, J. Z., Teoh, H., Quan, A., Glazer, S. A., Rotstein, O. D., Al-Omran, M. A., Verma, S., & Hess, D. A. (2021) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09669-7 · Cited by 30 · see citing works
Brill, A. L., Wisinski, J. A., Cadena, M. T., Thompson, M. F., Fenske, R. J., Brar, H. K., Schaid, M. D., Pasker, R. L., & Kimple, M. E. (2016) · Molecular Endocrinology · doi:10.1210/me.2015-1164 · Cited by 28 · see citing works
The Anti-Inflammatory Effect of Novel Antidiabetic Agents
Theofilis, P., Sagris, Μ., Oikonomou, E. K., Antonopoulos, A. S., Siasos, G., Tsioufis, K., & Tousoulis, D. (2022) · Life · doi:10.3390/life12111829 · Cited by 31 · see citing works
Benefits of healthy adipose tissue in the treatment of diabetes
Gunawardana, S. C. (2014) · World Journal of Diabetes · doi:10.4239/wjd.v5.i4.420 · Cited by 24 · see citing works
Exendin-4 protects rat islets against loss of viability and function induced by brain death
Carlessi, R., Lemos, N. E., Dias, A. L., de Oliveira, F. S., Brondani, L. D. A., Canani, L. H. S., Bauer, A. C., Leitão, C. B., & Crispim, D. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.05.009 · Cited by 23 · see citing works
The role of incretins and incretin-based drugs in autoimmune diseases
Radbakhsh, S., Atkin, S. L., Simental‐Mendía, L. E., & Sahebkar, A. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107845 · Cited by 24 · see citing works
Capitini, C. M., Nasholm, N. M., Chien, C. D., Larabee, S. M., Qin, H., Song, Y. K., Klover, P. J., Hennighausen, L. G., Khan, J., & Fry, T. J. (2014) · Blood · doi:10.1182/blood-2013-05-500876 · Cited by 20 · see citing works
Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice
He, L., Law, P. T. Y., Wong, C. K., Chan, J. C. N., & Chan, P. K. S. (2017) · Scientific Reports · doi:10.1038/s41598-017-01952-5 · Cited by 19 · see citing works
Zhao, M., Liao, B., Yun, C., Qi, X., & Pang, Y. (2024) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-024-01269-9 · Cited by 16 · see citing works
Jeong, J., Yook, S., Jung, Y., Im, B.-H., Lee, M., Ahn, C., Lee, D. Y., & Byun, Y. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.01.029 · Cited by 15 · see citing works
Li, B., Bi, C. L., Lang, N., Li, Y. Z., Xu, C., Zhang, Y. Q., Zhai, A. X., & Cheng, Z. F. (2014) · Molecular Biology Reports · doi:10.1007/s11033-013-3016-2 · Cited by 15 · see citing works
Luo, X., Pan, L., Nie, A., Wang, Q., Gu, Y., Li, F., Zhang, H., Li, W., & Li, X. (2013) · Journal of Diabetes · doi:10.1111/1753-0407.12061 · Cited by 14 · see citing works
He, S., Wu, W., Wan, Y., Nandakumar, K. S., Cai, X., Tang, X., Liu, S., & Yao, X. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01230 · Cited by 12 · see citing works
Incretins: B eyond type 2 diabetes
Dandona, P., Ghanim, H., & Chaudhuri, A. (2018) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13153 · Cited by 12 · see citing works
The Regulation Role of the Gut-Islets Axis in Diabetes
Yang, S., Cao, J., Sun, C., & Li, Y. (2024) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s455026 · Cited by 9 · see citing works
Adipose Tissue, Hormones, and Treatment of Type 1 Diabetes
Gunawardana, S. C. (2012) · Current Diabetes Reports · doi:10.1007/s11892-012-0300-9 · Cited by 8 · see citing works
Henriksen, K., Rufer, C., Title, A. C., Jawurek, S., Hartmann, B., Holst, J. J., Knop, F. K., Yesildag, B., & Størling, J. (2025) · Diabetologia · doi:10.1007/s00125-025-06425-3 · Cited by 7 · see citing works
He, X., Zhao, Z., Sun, Y., & Jiang, X. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118163 · Cited by 7 · see citing works
Mizukami, H., Inaba, W., Takahashi, K., Kamata, K., Tsuboi, K., & Yagihashi, S. (2013) · Pancreas · doi:10.1097/mpa.0b013e318287c9b5 · Cited by 7 · see citing works
Baden, M. Y., Fukui, K., Hosokawa, Y., Iwahashi, H., Imagawa, A., & Shimomura, I. (2015) · PLoS ONE · doi:10.1371/journal.pone.0144606 · Cited by 6 · see citing works
Gao, H., Zhao, Q., Tang, S., Li, K., Qin, F., Song, Z., Pan, Y., Jin, L., & Zhang, Y. (2021) · Scientific Reports · doi:10.1038/s41598-021-83201-4 · Cited by 5 · see citing works
Expression kinetics reveal the self-adaptive role of β cells during the progression of diabetes
Srivastava, S., Pandey, H. K., & Tripathi, Y. B. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.06.168 · Cited by 5 · see citing works
Antagonistic Effect and In Vitro Activity of Dauricine on Glucagon Receptor
Li, L., Dai, S., Liu, J., Wu, W., Zhao, Q.-X., Wang, X., Wang, N., & Xu, Z. (2022) · Journal of Natural Products · doi:10.1021/acs.jnatprod.2c00446 · Cited by 5 · see citing works
Gut Hormones and Inflammatory Bowel Disease
Weng, J., & Lo, C. C. (2025) · Biomolecules · doi:10.3390/biom15071013 · Cited by 3 · see citing works
Predicting response to incretin-based therapy
Kalra, S., Kalra, B., Sahay, R. K., & Agrawal, N. K. (2011) · Research and Reports in Endocrine Disorders · doi:10.2147/rred.s16282 · Cited by 3 · see citing works
Niu, B., Li, C., Su, H., Li, Q., He, Q., Liu, L., Xue, Y., Shen, T., & Xia, X. (2017) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2017.4803 · Cited by 2 · see citing works
GLP-1 Can Protect Proinflammatory Cytokines Induced Beta Cell Apoptosis through the Ubiquitination
Lim, D. M., Kim, J., Lee, K. W., Park, K. Y., & Kim, B. J. (2011) · Endocrinology and Metabolism · doi:10.3803/enm.2011.26.2.142
The Acute Regulation of Intestinal Chylomicron Secretion by Glucagon-like Peptides
Hsieh, J. (2012) · TSpace (University of Toronto)
- Authors
- Pugazhenthi, U., Velmurugan, K., Tran, A., Mahaffey, G., & Pugazhenthi, S.
- Affiliations
- University of Colorado Denver (US)
- Veterans Health Administration (US)
- Corresponding author
- Pugazhenthi, S.
- Venue
- Diabetologia
- Published
- 2010-07-16
- Volume
- 53
- Issue
- 11
- Pages
- 2357-2368
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2007907433
- Cited by
- 61
- References
- 52
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 5 · 2014: 7 · 2013: 10 · 2012: 7
- FWCI
- 7.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association (1-06-JF-40)
- U.S. Department of Veterans Affairs (I01 BX001837)
- University of Denver
- University of Colorado Denver
- 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 › Genetics › Diabetes and associated disorders
- Keywords
- exendin-4, glucagon-like peptide-1 analogues, anti-inflammatory activity, human pancreatic islets, CXCL10, chemokines, type 1 diabetes, insulitis, interferon-gamma, STAT1, phosphodiesterase inhibitors, cyclic AMP, forskolin, MIN6 cells, beta cell inflammation, cytokine synergy
- MeSH terms
- Exenatide, Cyclic AMP, Analysis of Variance, Anti-Inflammatory Agents, Cell Line, Cells, Cultured, Diabetes Mellitus, Enzyme-Linked Immunosorbent Assay, Humans, Interferon-gamma, Islets of Langerhans, Peptides, Phosphodiesterase Inhibitors, RNA, Messenger, Tumor Necrosis Factor-alpha, Venoms, Blotting, Western, Signal Transduction, NF-kappa B, Reverse Transcriptase Polymerase Chain Reaction, STAT1 Transcription Factor, Interleukin-1beta, Chemokine CXCL10, 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
