Department of Endocrinology, The Second Affiliated Hospital of Guangzhou Medical University, The East Chang-Gang Road, Guangzhou, China.
Department of Endocrinology, The Second Affiliated Hospital of Guangzhou Medical University, The East Chang-Gang Road, Guangzhou, China.
Int Immunopharmacol. 2020 Nov;88:106945. doi: 10.1016/j.intimp.2020.106945. Epub 2020 Sep 23.
Dipeptidyl-peptidase 4 (DPP-4) inhibitor (sitagliptin) is a novel anti-hyperglycemia drug in the treatment of type 2 diabetes. However, its potential in type 1 diabetes is still unclear. Recent studies show that increased infection, especially respiratory tract infection, is significantly associated with DPP-4 inhibitors. In this study, we aimed to explore the effects of long-term inhibition of DPP- 4 on innate immunity in type 1 diabetes. Forty mice were randomly divided into 4 groups (n = 10 in each group): control group, lipopolysaccharide (LPS) group, sitagliptin group and sitagliptin + LPS group. The concentrations of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-α and IFN-γ were measured with Mesco Scale Discovery multiplexed-assay kit. Immunohistochemistry staining of pancreases was performed and insulitis scores for each islet were determined. The results showed that DPP-4 inhibition has no effect on incident rate of diabetes and metabolic parameters in NOD mice. Long-term inhibition of DPP-4 reduced CD4+T cells to infiltrate into islets and ameliorated insulitis in NOD mice. DPP-4 inhibition downregulated serum interleukin IL-1β and IL-12 in NOD mice. However, it had no significant effect on LPS-induced IL-1β, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in NOD mice. In conclusion, Long-term inhibition of DPP-4 exists anti-inflammatory effect in type 1 diabetes probably by reducing CD4+T cells to infiltrate into islets and downregulating L-1β and IL-12 in serum.
二肽基肽酶 4（DPP-4）抑制剂（西他列汀）是治疗 2 型糖尿病的新型抗高血糖药物。然而，其在 1 型糖尿病中的潜力尚不清楚。最近的研究表明，感染增加，特别是呼吸道感染，与 DPP-4 抑制剂显著相关。在这项研究中，我们旨在探讨长期抑制 DPP-4 对 1 型糖尿病固有免疫的影响。40 只小鼠被随机分为 4 组（每组 10 只）：对照组、脂多糖（LPS）组、西他列汀组和西他列汀+LPS 组。采用 Mesco Scale Discovery 多重分析试剂盒检测白细胞介素 1β（IL-1β）、白细胞介素 2（IL-2）、白细胞介素 4（IL-4）、白细胞介素 5（IL-5）、白细胞介素 6（IL-6）、白细胞介素 10（IL-10）、白细胞介素 12（IL-12）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的浓度。对胰腺进行免疫组织化学染色，并确定每个胰岛的胰岛炎评分。结果显示，DPP-4 抑制对 NOD 小鼠糖尿病的发生率和代谢参数没有影响。长期抑制 DPP-4 可减少 CD4+T 细胞浸润胰岛，并改善 NOD 小鼠的胰岛炎。DPP-4 抑制降低了 NOD 小鼠血清中白细胞介素 IL-1β 和 IL-12 的水平。然而，它对 NOD 小鼠中 LPS 诱导的 IL-1β、IL-6、IL-10、IL-12、肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ没有显著影响。综上所述，长期抑制 DPP-4 在 1 型糖尿病中存在抗炎作用，可能是通过减少 CD4+T 细胞浸润胰岛并降低血清中 IL-1β 和 IL-12 的水平实现的。
