Targeting the NLRP3 inflammasome-IL-1β pathway in type 2 diabetes and obesity.

IF 8.4 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Daniel T Meier, Joyce de Paula Souza, Marc Y Donath
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Abstract

Increased activity of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome-IL-1β pathway is observed in obesity and contributes to the development of type 2 diabetes and its complications. In this review, we describe the pathological activation of IL-1β by metabolic stress, ageing and the microbiome and present data on the role of IL-1β in metabolism. We explore the physiological role of the IL-1β pathway in insulin secretion and the relationship between circulating levels of IL-1β and the development of diabetes and associated diseases. We highlight the paradoxical nature of IL-1β as both a friend and a foe in glucose regulation and provide details on clinical translation, including the glucose-lowering effects of IL-1 antagonism and its impact on disease modification. We also discuss the potential role of IL-1β in obesity, Alzheimer's disease, fatigue, gonadal dysfunction and related disorders such as rheumatoid arthritis and gout. Finally, we address the safety of NLRP3 inhibition and IL-1 antagonists and the prospect of using this therapeutic approach for the treatment of type 2 diabetes and its comorbidities.

Abstract Image

针对 2 型糖尿病和肥胖症的 NLRP3 炎性体-IL-1β 通路。
肥胖症患者的NACHT、LRR和PYD结构域含蛋白3(NLRP3)炎性体-IL-1β通路的活性会增加,并导致2型糖尿病及其并发症的发生。在这篇综述中,我们描述了新陈代谢压力、老化和微生物组对 IL-1β 的病理性激活,并提供了有关 IL-1β 在新陈代谢中作用的数据。我们探讨了 IL-1β 通路在胰岛素分泌中的生理作用,以及循环中 IL-1β 水平与糖尿病及相关疾病发展之间的关系。我们强调了 IL-1β 在血糖调节中亦敌亦友的矛盾性质,并提供了临床转化的详细信息,包括 IL-1 拮抗剂的降糖效果及其对疾病改变的影响。我们还讨论了 IL-1β 在肥胖、阿尔茨海默病、疲劳、性腺功能障碍以及类风湿性关节炎和痛风等相关疾病中的潜在作用。最后,我们讨论了 NLRP3 抑制剂和 IL-1 拮抗剂的安全性,以及使用这种治疗方法治疗 2 型糖尿病及其合并症的前景。
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来源期刊
Diabetologia
Diabetologia 医学-内分泌学与代谢
CiteScore
18.10
自引率
2.40%
发文量
193
审稿时长
1 months
期刊介绍: Diabetologia, the authoritative journal dedicated to diabetes research, holds high visibility through society membership, libraries, and social media. As the official journal of the European Association for the Study of Diabetes, it is ranked in the top quartile of the 2019 JCR Impact Factors in the Endocrinology & Metabolism category. The journal boasts dedicated and expert editorial teams committed to supporting authors throughout the peer review process.
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