| Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. | |
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MedLine Citation:
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PMID: 20835230 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Seth L Masters; Aisling Dunne; Shoba L Subramanian; Rebecca L Hull; Gillian M Tannahill; Fiona A Sharp; Christine Becker; Luigi Franchi; Eiji Yoshihara; Zhe Chen; Niamh Mullooly; Lisa A Mielke; James Harris; Rebecca C Coll; Kingston H G Mills; K Hun Mok; Philip Newsholme; Gabriel Nuñez; Junji Yodoi; Steven E Kahn; Ed C Lavelle; Luke A J O'Neill |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-09-12 |
Journal Detail:
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Title: Nature immunology Volume: 11 ISSN: 1529-2916 ISO Abbreviation: Nat. Immunol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-21 Completed Date: 2010-11-03 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 100941354 Medline TA: Nat Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 897-904 Citation Subset: IM |
Affiliation:
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Immunology Research Centre, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland. smasters@tcd.ie |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amyloid
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metabolism* Animals Carrier Proteins / antagonists & inhibitors, genetics, metabolism* Cells, Cultured Dendritic Cells / immunology, metabolism Diabetes Mellitus, Type 2 / immunology*, metabolism Glyburide / pharmacology Humans Hypoglycemic Agents / pharmacology Interleukin-1beta / metabolism* Islet Amyloid Polypeptide Islets of Langerhans / metabolism Macrophages / immunology, metabolism Mice Mice, Inbred C57BL Mice, Transgenic Rats |
| Grant Support | |
ID/Acronym/Agency:
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AI063331/AI/NIAID NIH HHS; DK-75998/DK/NIDDK NIH HHS; R01 DK075998-03/DK/NIDDK NIH HHS; R01 DK075998-04/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amyloid; 0/Carrier Proteins; 0/Hypoglycemic Agents; 0/Interleukin-1beta; 0/Islet Amyloid Polypeptide; 0/NLRP3 protein, human; 10238-21-8/Glyburide |
| Comments/Corrections | |
Comment In:
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Nat Immunol. 2010 Oct;11(10):881-3
[PMID:
20856216
]
Cell Metab. 2010 Nov 3;12(5):427-8 [PMID: 21035753 ] Nat Rev Immunol. 2010 Nov;10(11):748 [PMID: 21080610 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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