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Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes
Open accessAbstract
Interleukin 1β (IL-1β) is an important inflammatory mediator of type 2 diabetes. Here we show that oligomers of islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas during type 2 diabetes, triggered the NLRP3 inflammasome and generated mature IL-1β. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1β production in vitro. Processing of IL-1β initiated by IAPP first required priming, a process that involved glucose metabolism and was facilitated by minimally oxidized low-density lipoprotein. Finally, mice transgenic for human IAPP had more IL-1β in pancreatic islets, which localized together with amyloid and macrophages. Our findings identify previously unknown mechanisms in the pathogenesis of type 2 diabetes and treatment of pathology caused by IAPP.
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“that induce interleukin (IL)-1β release to recruit macrophages and enhance local islet inflammation ( 45 ).”
From β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment (2014) · cites this paper as [45]
Experimental — accuracy not yet measuredIn the citing paper
“A potential role for NLRP3 in promoting elevated levels of IL-1β in type 2 diabetes was also implied by the observation of NLRP3-dependent IL-1β secretion by mouse bone marrow-derived macrophages and dendritic cells in response to islet amyloid polypeptide (IAPP), which is deposited in the pancreas and associated with loss of β-cell function in type 2 diabetes61.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [61]
In the citing paper
“Interestingly, the anti-diabetic drug glyburide (Glibenclamide; Roche/Sanofi-Aventis) has been shown to block glucose-mediated secretion of IL-1β by mouse pancreatic islets62, as well as IL-1β production by macrophages in response to IAPP61, and NLRP3-deficient mice were more glucose tolerant than wild-type mice62.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [61]
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“In a separate study, no differences in IL-1β secretion were observed between wild-type and TXNIP-deficient bone marrow-derived macrophages in response to several NLRP3 stimuli, including MSU crystals and ATP61.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [61]
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“However, the role of TXNIP and ROS in NLRP3 activation has been challenged.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [61]
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Citations
Cites
Mechanisms linking obesity to insulin resistance and type 2 diabetes
Kahn, S. E., Hull, R. L., & Utzschneider, K. M. (2006) · Nature · doi:10.1038/nature05482 · Cited by 5,448
Self-citationGout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026
Self-citationTLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690
Bauernfeind, F. G., Horvath, G. L., Stutz, A., Alnemri, E. S., MacDonald, K. L., Speert, D. P., Fernandes‐Alnemri, T., Wu, J., Monks, B. G., Fitzgerald, K. A., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901363 · Cited by 3,087
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., & Latz, E. (2008) · Nature Immunology · doi:10.1038/ni.1631 · Cited by 3,065
Thioredoxin-interacting protein links oxidative stress to inflammasome activation
Zhou, R., Tardivel, A., Thorens, B., Choi, I., & Tschopp, J. (2010) · Nature Immunology · doi:10.1038/ni.1831 · Cited by 2,708
Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
Dostert, C., Pétrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., & Tschopp, J. (2008) · Science · doi:10.1126/science.1156995 · Cited by 2,658
The NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441
Interleukin-1-receptor antagonist in type 2 diabetes mellitus
Larsen, C. M., Faulenbach, M., Vaag, A., Vølund, A., Ehses, J. A., Seifert, B., Mandrup-Poulsen, T., & Donath, M. Y. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa065213 · Cited by 1,798
Inflammatory Cytokines and the Risk to Develop Type 2 Diabetes
Spranger, J., Kroke, A., Möhlig, M., Hoffmann, K., Bergmann, M. M., Ristow, M., Boeing, H., & Pfeiffer, A. F. H. (2003) · Diabetes · doi:10.2337/diabetes.52.3.812 · Cited by 1,493
Cooper, G. J., Willis, A. C., Clark, A., Turner, R. C., Sim, R. B., & Reid, K. B. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.23.8628 · Cited by 1,299
Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets
Maedler, K., Sergeev, P., Ris, F., Oberholzer, J., Joller‐Jemelka, H. I., Spinas, G. A., Kaiser, N., Halban, P. A., & Donath, M. Y. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15318 · Cited by 1,141
Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets
Maedler, K., Sergeev, P., Ris, F., Oberholzer, J., Joller‐Jemelka, H. I., Spinas, G. A., Kaiser, N., Halban, P. A., & Donath, M. Y. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92172 · Cited by 1,113
Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets
Maedler, K., Sergeev, P., Ris, F., Oberholzer, J., Joller‐Jemelka, H. I., Spinas, G. A., Kaiser, N., Halban, P. A., & Donath, M. Y. (2002) · Journal of Clinical Investigation · doi:10.1172/jci200215318 · Cited by 1,006
Westermark, P., Wernstedt, C., Wilander, E., Hayden, D. W., O'Brien, T. D., & Johnson, K. H. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.11.3881 · Cited by 976
Techniques to study amyloid fibril formation in vitro
NILSSON, M. (2004) · Methods · doi:10.1016/j.ymeth.2004.03.012 · Cited by 968
Active Caspase-1 Is a Regulator of Unconventional Protein Secretion
Keller, M., Rüegg, A., Werner, S., & Beer, H. (2008) · Cell · doi:10.1016/j.cell.2007.12.040 · Cited by 851
Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus
Lorenzo, A., Razzaboni, B. L., Weir, G. C., & Yankner, B. A. (1994) · Nature · doi:10.1038/368756a0 · Cited by 820
Glyburide inhibits the Cryopyrin/Nalp3 inflammasome
Lamkanfi, M., Mueller, J. L., Vitari, A. C., Misaghi, S., Fedorova, A., Deshayes, K., Lee, W. P., Hoffman, H. M., & Dixit, V. M. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200903124 · Cited by 820
Janson, J., Ashley, R. H., Harrison, D. J., McIntyre, S., & Butler, P. C. (1999) · Diabetes · doi:10.2337/diabetes.48.3.491 · Cited by 614
Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome
Sharp, F. A., Ruane, D., Claass, B., Creagh, E. M., Harris, J., Malyala, P., Singh, M., O’Hagan, D. T., Pétrilli, V., Tschopp, J., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804897106 · Cited by 536
Self-citationCytotoxicity of Human p I 7 Interleukin-1 for Pancreatic Islets of Langerhans
Bendtzen, K., Mandrup-Poulsen, T. R., Nerup, J., Nielsen, J. H., Dinarello, C. A., & Svenson, M. (1986) · Science · doi:10.1126/science.3086977 · Cited by 529
Clark, A., Wells, C. A., BULEY, I. D., Cruickshank, J. K., Vanhegan, R. I., Matthews, D. R., Cooper, G. J. S., Holman, R. R., & Turner, R. C. (1988) · PubMed · Cited by 518
Butler, A. E., Janson, J., Soeller, W. C., & Butler, P. C. (2003) · Diabetes · doi:10.2337/diabetes.52.9.2304 · Cited by 411
Miller, Y. I., Viriyakosol, S., Binder, C. J., Feramisco, J. R., Kirkland, T. N., & Witztum, J. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209634200 · Cited by 398
Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide.
Janson, J., Soeller, W. C., Roche, P. C., Nelson, R. T., Torchia, A. J., Kreutter, D. K., & Butler, P. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.14.7283 · Cited by 343
Böni‐Schnetzler, M., Thorne, J. T., Parnaud, G., Marselli, L., Ehses, J. A., Kerr-Conte, J. A., Pattou, F. N., Halban, P. A., Weir, G. C., & Donath, M. Y. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0396 · Cited by 327
Verchere, C. B., D'Alessio, D. A., Palmiter, R. D., Weir, G. C., Bonner-Weir, S., Baskin, D. G., & Kahn, S. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3492 · Cited by 278
Self-citationButler, A. E., Jang, J., Gurlo, T., Carty, M. D., Soeller, W. C., & Butler, P. C. (2004) · Diabetes · doi:10.2337/diabetes.53.6.1509 · Cited by 267
van de Veerdonk, F. L., Smeekens, S. P., Joosten, L. A. B., Kullberg, B. J., Dinarello, C. A., van der Meer, J. W. M., & Netea, M. G. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914795107 · Cited by 248
Interleukin-1β Secretion Is Impaired by Inhibitors of the Atp Binding Cassette Transporter, ABC1
Hamon, Y., Luciani, M., Becq, F., Verrier, B., Rubartelli, A., & Chimini, G. (1997) · Blood · doi:10.1182/blood.v90.8.2911 · Cited by 224
Zraika, S., Hull, R. L., Udayasankar, J., Aston‐Mourney, K., Subramanian, S. L., Kisilevsky, R., Szarek, W. A., & Kahn, S. E. (2009) · Diabetologia · doi:10.1007/s00125-008-1255-x · Cited by 215
Self-citationPharmacological Discrimination of Calcitonin Receptor: Receptor Activity-Modifying Protein Complexes
Hay, D. L., Christopoulos, G., Christopoulos, A., Poyner, D. R., & Sexton, P. M. (2005) · Molecular Pharmacology · doi:10.1124/mol.104.008615 · Cited by 213
Yates, S. L., Burgess, L. H., Kocsis‐Angle, J., Antal, J. M., Dority, M. D., Embury, P. B., Piotrkowski, A. M., & Brunden, K. R. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0741017.x · Cited by 202
Zraika, S., Hull, R. L., Verchere, C. B., Clark, A., Potter, K. J., Fraser, P. E., Raleigh, D. P., & Kahn, S. E. (2010) · Diabetologia · doi:10.1007/s00125-010-1671-6 · Cited by 191
Self-citationWidespread Amyloid Deposition in Transplanted Human Pancreatic Islets
Westermark, G. T., Westermark, P., Berne, C., & Korsgren, O. (2008) · New England Journal of Medicine · doi:10.1056/nejmc0802893 · Cited by 187
Njajou, O., Kanaya, A., Holvoet, P., Connelly, S. A., Strotmeyer, E., Harris, T. B., Cummings, S., & Hsueh, W. (2009) · Diabetes/Metabolism Research Reviews · doi:10.1002/dmrr.1011 · Cited by 178
Islet Amyloid Polypeptide (IAPP) Transgenic Rodents as Models for Type 2 Diabetes
Matveyenko, A. V., & Butler, P. C. (2006) · ILAR Journal · doi:10.1093/ilar.47.3.225 · Cited by 150
Abderrahmani, A., Niederhäuser, G., Favre, D., Abdelli, S., Ferdaoussi, M., Yang, J. Y., Regazzi, R., Widmann, C., & Waeber, G. (2007) · Diabetologia · doi:10.1007/s00125-007-0642-z · Cited by 147
Longitudinal studies on the development of diabetes in individual Macaca nigra
Howard, C. F. (1986) · Diabetologia · doi:10.1007/bf00452067 · Cited by 141
Welsh, N., Cnop, M., Kharroubi, I., Bugliani, M., Lupi, R., Marchetti, P., & Eizirik, D. L. (2005) · Diabetes · doi:10.2337/diabetes.54.11.3238 · Cited by 125
Hull, R. L., Andrikopoulos, S., Verchere, C. B., Vidal, J., Wang, F., Cnop, M., Prigeon, R. L., & Kahn, S. E. (2003) · Diabetes · doi:10.2337/diabetes.52.2.372 · Cited by 109
Self-citationRapid deposition of amyloid in human islets transplanted into nude mice
Westermark, P., Eizirik, D. L., PIPELEERS, D. G., Hellerstr�m, C., & Andersson, A. (1995) · Diabetologia · doi:10.1007/bf00400722 · Cited by 93
Wang, F., Hull, R. L., Vidal, J., Cnop, M., & Kahn, S. E. (2001) · Diabetes · doi:10.2337/diabetes.50.11.2514 · Cited by 77
Self-citationUdayasankar, J., Kodama, K., Hull, R. L., Zraika, S., Aston‐Mourney, K., Subramanian, S. L., Tong, J., Faulenbach, M. V., Vidal, J., & Kahn, S. E. (2008) · Diabetologia · doi:10.1007/s00125-008-1185-7 · Cited by 71
Self-citationEnhanced in vitro production of amyloid-like fibrils from mutant (S20G) islet amyloid polypeptide
Ma, Z., Westermark, G., Sakagashira, S., Sanke, T., Gustavsson, Å., Sakamoto, H., Engström, U., Nanjo, K., & Westermark, P. (2001) · Amyloid: Journal of Protein Folding Disorders · doi:10.3109/13506120108993820 · Cited by 69
S20G mutation of the amylin gene is associated with Type II diabetes in Japanese
Seino, S. (2001) · Diabetologia · doi:10.1007/s001250100531 · Cited by 68
Michalska, M., Wolf, G., Walther, R., & Newsholme, P. (2010) · Bioscience Reports · doi:10.1042/bsr20090138 · Cited by 61
Self-citationMacrophages and pancreatic islet amyloidosis
de Koning, E. J. P., van den Brand, J., Mott, V. L., CHARGÉ, S. B. P., Hansen, B. C., Bodkin, N. L., Morris, J. F., & Clark, A. (1998) · Amyloid · doi:10.3109/13506129809007297 · Cited by 42
Badman, M. K., Pryce, R. A., CHARGÉ, S. B. P., Morris, J. F., & Clark, A. (1998) · Cell and Tissue Research · doi:10.1007/s004410050998 · Cited by 36
Increased electronegative charge of serum low-density lipoprotein in patients with diabetes mellitus
Yano, M., Inoue, M., Maehata, E., Shiba, T., Yamakado, M., Hirabayashi, Y., Taniyama, M., & Suzuki, S. (2003) · Clinica Chimica Acta · doi:10.1016/j.cccn.2003.09.020 · Cited by 28
Human Amylin Stimulates Inflammatory Cytokine Secretion from Human Glioma Cells
Gitter, B. D., Cox, L. M., Carlson, C. D., & May, P. C. (2000) · NeuroImmunoModulation · doi:10.1159/000026432 · Cited by 19
Apolinário, E., Ferderbar, S., Pereira, E. C., Bertolami, M. C., Faludi, A. Á., Monte, O., Gagliardi, A. R. D. T., Xavier, H. T., & Abdalla, D. S. P. (2006) · Cited by 16
Russell, J. C., & Proctor, S. D. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707226 · Cited by 9
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Succinate is an inflammatory signal that induces IL-1β through HIF-1α
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., et al. (2013) · Nature · doi:10.1038/nature11986 · Cited by 4,176
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Donath, M. Y., & Shoelson, S. E. (2011) · Nature Reviews Immunology · doi:10.1038/nri2925 · Cited by 3,737
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Kelley, N., Jeltema, D., Duan, Y., & He, Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133328 · Cited by 3,539
“However, a different study found that TXNIP is dispensable for NLRP3 inflammasome activation that is induced by ATP, MSU, and islet amyloid polypeptide [159].”
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Metadata
- Authors
- Masters, S. L., Dunne, A., Subramanian, S. L., Hull, R. L., Tannahill, G. M., Sharp, F. A., Becker, C., Franchi, L., Yoshihara, E., Chen, Z., Mullooly, N., Mielke, L. A., Harris, J., Coll, R. C., Mills, K. H. G., Mok, K. H., Newsholme, P., Nuñez, G., Yodoi, J., Kahn, S. E., Lavelle, E. C., & O'Neill, L. A. J.
- Affiliations
- Trinity College Dublin (IE)
- University of Washington (US)
- University of Michigan (US)
- Kyoto University (JP)
- University College Dublin (IE)
- Corresponding author
- Masters, Seth L
- ORCID
- Venue
- Nature Immunology
- Published
- 2010-09-12
- Volume
- 11
- Issue
- 10
- Pages
- 897-904
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3103663
- OpenAlex
- W2034946303
- Cited by
- 1,330
- References
- 55
- Citations by year
- 2026: 58 · 2025: 57 · 2024: 64 · 2023: 75 · 2022: 71 · 2021: 99 · 2020: 100 · 2019: 95 · 2018: 82 · 2017: 83 · 2016: 73 · 2015: 101 · 2014: 95 · 2013: 112 · 2012: 83
- FWCI
- 35.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- eSpace (Curtin University) (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI063331, R56AI063331, R01AI063331, R37AI063331)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-75998, R01DK075998)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- NLRP3 inflammasome, amylin, IL-1β, type 2 diabetes, beta cell destruction, glibenclamide, LDL oxidation, glucose metabolism, inflammasome priming, pancreatic islets, macrophages, amyloid deposition
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Amyloid, Animals, Carrier Proteins, Cells, Cultured, Dendritic Cells, Diabetes Mellitus, Type 2, Glyburide, Humans, Hypoglycemic Agents, Islets of Langerhans, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Cytoplasmic and Nuclear, Mice, Rats, Interleukin-1beta, Islet Amyloid Polypeptide
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