Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1ß 2 in type 2 diabetes
Interleukin 1ß 2 (IL-1ß 2) 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-1ß 2. One thera...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
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Nature Publishing Group
2010
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| Online Access: | http://hdl.handle.net/20.500.11937/6738 |
| _version_ | 1848745163104452608 |
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| author | Masters, S. Dunne, A. Subramanian, S. Hull, R. Tannahill, G. Sharp, F. Becker, C. Franchi, L. Yoshihara, E. Chen, Z. Mullooly, N. Mielke, L. Harris, J. Coll, R. Mills, K. Mok, K. Newsholme, Philip Nuñez, G. Yodoi, J. Kahn, S. Lavelle, E. O'Neill, L. |
| author_facet | Masters, S. Dunne, A. Subramanian, S. Hull, R. Tannahill, G. Sharp, F. Becker, C. Franchi, L. Yoshihara, E. Chen, Z. Mullooly, N. Mielke, L. Harris, J. Coll, R. Mills, K. Mok, K. Newsholme, Philip Nuñez, G. Yodoi, J. Kahn, S. Lavelle, E. O'Neill, L. |
| author_sort | Masters, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Interleukin 1ß 2 (IL-1ß 2) 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-1ß 2. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1ß 2 production in vitro. Processing of IL-1ß 2 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-1ß 2 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. |
| first_indexed | 2025-11-14T06:12:59Z |
| format | Journal Article |
| id | curtin-20.500.11937-6738 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:12:59Z |
| publishDate | 2010 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-67382018-03-29T09:05:43Z Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1ß 2 in type 2 diabetes Masters, S. Dunne, A. Subramanian, S. Hull, R. Tannahill, G. Sharp, F. Becker, C. Franchi, L. Yoshihara, E. Chen, Z. Mullooly, N. Mielke, L. Harris, J. Coll, R. Mills, K. Mok, K. Newsholme, Philip Nuñez, G. Yodoi, J. Kahn, S. Lavelle, E. O'Neill, L. Interleukin 1ß 2 (IL-1ß 2) 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-1ß 2. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1ß 2 production in vitro. Processing of IL-1ß 2 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-1ß 2 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. 2010 Journal Article http://hdl.handle.net/20.500.11937/6738 10.1038/ni.1935 Nature Publishing Group restricted |
| spellingShingle | Masters, S. Dunne, A. Subramanian, S. Hull, R. Tannahill, G. Sharp, F. Becker, C. Franchi, L. Yoshihara, E. Chen, Z. Mullooly, N. Mielke, L. Harris, J. Coll, R. Mills, K. Mok, K. Newsholme, Philip Nuñez, G. Yodoi, J. Kahn, S. Lavelle, E. O'Neill, L. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1ß 2 in type 2 diabetes |
| title | Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1ß 2 in type 2 diabetes |
| title_full | Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1ß 2 in type 2 diabetes |
| title_fullStr | Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1ß 2 in type 2 diabetes |
| title_full_unstemmed | Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1ß 2 in type 2 diabetes |
| title_short | Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1ß 2 in type 2 diabetes |
| title_sort | activation of the nlrp3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced il-1ß 2 in type 2 diabetes |
| url | http://hdl.handle.net/20.500.11937/6738 |