Targeting the NLRP3 Inflammasome-IL-1β Pathway in Type 2 Diabetes and Obesity

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2024 Nov 4

PMID 39496966

Authors

Daniel T Meier

Joyce de Paula Souza

Marc Y Donath

Affiliations

Soon will be listed here.

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.

Citing Articles

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Zuriaga M, Fuster J Diabetologia. 2025; .

PMID: 40064675 DOI: 10.1007/s00125-025-06393-8.

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