Department of Prophylaxis of Metabolic Diseases, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences in Olsztyn, Białystok, Poland.
Endocr Metab Immune Disord Drug Targets. 2024;24(6):611-616. doi: 10.2174/1871530323666230911114150.
Insulin resistance, i.e., decreased biological response to insulin, is a risk factor for many diseases, such as obesity, type 2 diabetes (T2DM), cardiovascular disease, polycystic ovary syndrome, some forms of cancer and neurodegenerative diseases. One of its main causes is chronic low-grade inflammation, mediated by the proinflammatory pathways, such as the c-Jun N-terminal kinase (JNK) pathway and the nuclear factor kappa B (NFκB) pathway. Interleukin (IL)-38 (IL-38) is a newly discovered cytokine that belongs to the IL-1 family. There are three hypothetical pathways through which IL-38 may bind to the specific receptors and inhibit their proinflammatory activity. Those pathways are associated with IL-36 receptor (IL-36R), IL-1 receptor accessory protein-like 1 (IL1RAPL1) and IL-1 receptor 1 (IL1R1). There are studies linking IL-38 to improve insulin sensitivity through the difference in serum IL-38 in patients with insulin resistance or the correlation of IL-38 concentrations with insulin resistance indexes. However, many questions still remain regarding the biological activity of IL-38 itself and its role in the pathogenesis of insulin resistance. The goal of this study is to showcase IL-38, its biological activity, hypothesized signaling pathways, connection with insulin resistance and future perspectives of research on IL-38. We present that IL-38 associated signaling can be a potential target for the treatment of insulin resistance and associated diseases.
胰岛素抵抗，即胰岛素生物反应降低，是许多疾病的风险因素，如肥胖、2 型糖尿病（T2DM）、心血管疾病、多囊卵巢综合征、某些形式的癌症和神经退行性疾病。其主要原因之一是慢性低度炎症，由促炎途径介导，如 c-Jun N-末端激酶（JNK）途径和核因子 kappa B（NFκB）途径。白细胞介素（IL）-38（IL-38）是一种新发现的细胞因子，属于 IL-1 家族。有三种假设途径，IL-38 可以通过这些途径与特定受体结合并抑制其促炎活性。这些途径与 IL-36 受体（IL-36R）、IL-1 受体辅助蛋白样 1（IL1RAPL1）和 IL-1 受体 1（IL1R1）有关。有研究表明，IL-38 通过胰岛素抵抗患者血清中 IL-38 的差异或 IL-38 浓度与胰岛素抵抗指标的相关性，与改善胰岛素敏感性有关。然而，关于 IL-38 本身的生物学活性及其在胰岛素抵抗发病机制中的作用，仍有许多问题尚待解决。本研究的目的是展示 IL-38、其生物学活性、假设的信号通路、与胰岛素抵抗的联系以及 IL-38 研究的未来前景。我们提出，IL-38 相关信号通路可能是治疗胰岛素抵抗和相关疾病的潜在靶点。
