期刊
IMMUNOLOGY AND CELL BIOLOGY
卷 92, 期 4, 页码 314-323出版社
WILEY
DOI: 10.1038/icb.2014.4
关键词
inflammation; macrophage; NLRP3 inflammasome; pancreatic beta; pancreatic islet; Toll-like receptor
资金
- Child and Family Research Institute
- University of British Columbia
- Canadian Foundation for Innovation
- Canadian Diabetes Association
- Canadian Institutes of Health Research and Servier
- Child and Family Research Institute investigator award
- Canadian Diabetes Association scholar award
- CIHR-Vanier Canada Graduate Scholarship
- UBC transplantation Training Program
The global health and economic burden of type 2 diabetes (T2D) has reached staggering proportions. Current projections estimate that 592 million people will have diabetes by 2035. T2D-which comprises 90% of cases-is a complex disease, in most cases resulting from a combination of predisposing genes and an unhealthy environment. Clinical onset of the disease occurs when pancreatic beta cells fail in the face of insulin resistance. It has long been appreciated that chronic activation of the innate immune system is associated with T2D, and many organs critical to the regulation of glucose homeostasis show signs of a chronic inflammatory process, including the pancreatic islets of Langerhans. Recent clinical trials using IL-1-targeting agents have confirmed that inflammation contributes to beta-cell failure in humans with T2D. However, little is known about the nature of the pro-inflammatory response within the islet, and there is considerable debate about the triggers for islet inflammation, which may be systemically derived and/or tissue-specific. In this review, we present evidence that Toll-like receptors 2 and 4 and the NLRP3 (Nucleotide-binding oligomerization domain, Leucine-rich Repeat and Pyrin domain containing 3) inflammasome are triggers for islet inflammation in T2D and propose that the activation of macrophages by these triggers mediates islet endocrine cell dysfunction. Therapeutically targeting these receptors may improve hyperglycemia and protect the beta cell in T2D.
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