Interleukin-1 beta targeted therapy for type 2 diabetes

被引:108
作者
Maedler, Kathrin [1 ]
Dharmadhikari, Gitanjali [1 ]
Schumann, Desiree M. [2 ]
Storling, Joachim [3 ]
机构
[1] Univ Bremen, Ctr Biomol Interact Bremen, Islet Biol Lab, D-28359 Bremen, Germany
[2] Boehringer Ingelheim GmbH & Co KG, Cardiometab Dis Res, Biberach, Germany
[3] Hagedorn Res Inst, Gentofte, Denmark
关键词
diabetes; IL-1Ra; IL-1; beta; beta-cell; BETA-CELL DEATH; IL-1 RECEPTOR ANTAGONIST; ENDOPLASMIC-RETICULUM STRESS; PANCREATIC-ISLET TRANSPLANTATION; CYTOKINE-INDUCED APOPTOSIS; ADENOVIRAL GENE-TRANSFER; JUN NH2-TERMINAL KINASE; TUMOR-NECROSIS-FACTOR; DIET-INDUCED OBESITY; ISOLATED RAT ISLETS;
D O I
10.1517/14712590903136688
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Since having been cloned in 1984, IL-1 beta has been the subject of over 22,000 citations in Pubmed, among them over 800 reviews. This is because of its numerous effects. IL-1 beta is a regulator of the body's inflammatory response and is produced after infection, injury, and antigenic challenge. It plays a role in various diseases, including autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases and type 1 diabetes, as well as in diseases associated with metabolic syndrome such as atherosclerosis, chronic heart failure and type 2 diabetes. Macrophage are the primary source of IL-1, but epidermal, epithelial, lymphoid and vascular tissues also synthesize IL-1. IL-1 beta production and secretion have also been reported from pancreatic islets. Insulin-producing beta-cells within pancreatic islets are specifically prone to IL-beta-induced destruction and loss of function. Macrophage-derived IL-1 beta production in insulin-sensitive organs, leads to progression of inflammation and induction of insulin resistance in obesity. We summarize the mechanisms involved in inflammation and specifically the IL-1 beta signals that lead to the progression of insulin resistance and diabetes. We highlight recent clinical studies and experiments in animals and isolated islets using IL-1 beta as a potential target for the therapy of type 2 diabetes.
引用
收藏
页码:1177 / 1188
页数:12
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