Deciphering interleukin‐18 in diabetes and its complications: Biological features, mechanisms, and therapeutic perspectives

• Published in: Obesity reviews 2024-11, Vol.25 (11), p.e13818-n/a
• Main Authors: Gui, Runlin, Ren, Yuanyuan, Wang, Zhen, Li, Yang, Wu, Chengsong, Li, Xiaofang, Li, Man, Li, Yujia, Qian, Lu, Xiong, Yuyan
• Format: Article
• Language: English
• Subjects: Animals; Beta cells; Cell death; Cytokines; death; Diabetes; Diabetes Complications; Diabetes Mellitus; diabetic complications; Diagnosis; Humans; Immune system; Inflammation; Inhibitors; Insulin; Insulin Resistance; Insulin-Secreting Cells - metabolism; Interleukin-18 - metabolism; Interleukins; Interleukin‐18; Medical diagnosis; Mortality; Nitric oxide; obesity; Pancreatitis; Pathogenesis; Signal Transduction; therapeutics; β‐cell death; β‐cell failure
• ISSN: 1467-7881; 1467-789X; 1467-789X
• DOI: 10.1111/obr.13818

Summary Interleukin‐18 (IL‐18), a potent and multifunctional pro‐inflammatory cytokine, plays a critical role in regulating β‐cell failure, β‐cell death, insulin resistance, and various complications of diabetes mellitus (DM). It exerts its effects by triggering various signaling pathways, enhancing the production of pro‐inflammatory cytokines and nitric oxide (NO), as well as promoting immune cells infiltration and β‐cells death. Abnormal alterations in IL‐18 levels have been revealed to be strongly associated with the onset and development of DM and its complications. Targeting IL‐18 may present a novel and promising approach for DM therapy. An increasing number of IL‐18 inhibitors, including chemical and natural inhibitors, have been developed and have been shown to protect against DM and diabetic complications. This review provides a comprehensive understanding of the production, biological functions, action mode, and activated signaling pathways of IL‐18. Next, we shed light on how IL‐18 contributes to the pathogenesis of DM and its associated complications with links to its roles in the modulation of β‐cell failure and death, insulin resistance in various tissues, and pancreatitis. Furthermore, the therapeutic potential of targeting IL‐18 for the diagnosis and treatment of DM is also highlighted. We hope that this review will help us better understand the functions of IL‐18 in the pathogenesis of DM and its complications, providing novel strategies for DM diagnosis and treatment. DM is one of the most common chronic metabolic diseases caused by β‐cells β‐cell dysfunction and insulin resistance. IL‐18 contributes to the progression of DM and its complications by inducing β‐cells failure and death, insulin resistance, and pancreatitis. IL‐18 orchestrates β‐cell failure and death, insulin resistance, and pancreatitis through modulation of IL‐18‐related signaling pathway, inflammatory responses, NO production, and immune cells infiltration.