Dipeptidyl peptidase-4 (DPP4) inhibitor sitagliptin alleviates liver inflammation of diabetic mice by acting as a ROS scavenger and inhibiting the NFκB pathway.
Dipeptidyl peptidase-4 (DPP4) inhibitor sitagliptin alleviates liver inflammation of diabetic mice by acting as a ROS scavenger and inhibiting the NFκB pathway.
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二肽基肽酶 4 (DPP4) 抑制剂西格列汀通过充当 ROS 清除剂和抑制 NFκB 通路来减轻糖尿病小鼠的肝脏炎症。
DOI：
10.1038/s41420-021-00625-7
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发表时间：
2021-09-07
影响因子：
7
通讯作者：
Zhao D
中科院分区：
文献类型：
--
作者：
Wang X;Ke J;Zhu YJ;Cao B;Yin RL;Wang Y;Wei LL;Zhang LJ;Yang LY;Zhao D
作为一种常见的慢性代谢性疾病，糖尿病的发生发展还可能伴随肝脏损害和炎症性疾病。西格列汀是二肽基肽酶-4（DPP 4，也称为CD 26）的抑制剂，临床上用于DM治疗。然而，西格列汀在肝脏疾病中的有效性机制在很大程度上是未知的。在这项研究中，患有链脲佐菌素（STZ）的小鼠表现出肝脏DPP 4表达和活性升高，以及炎症和慢性肝损伤表型，而西格列汀特异性抑制小鼠肝组织和肝细胞中DPP 4的活性有助于减少STZ诱导的糖尿病小鼠中的细胞因子，氧化应激，细胞凋亡和炎症。此外，在HepG 2细胞或原代小鼠肝细胞中，西格列汀可降低TNFα或LPS诱导的细胞活性氧（ROS）水平、细胞凋亡和NFκB信号通路中的蛋白表达。总之，我们的研究证实西格列汀可以通过减轻ROS产生和NFκB信号激活来保护肝组织，为预防糖尿病肝病的发展提供了一种假定的机制。
As a common chronic metabolic disease, the development of diabetes mellitus (DM) may also be accompanied by liver damage and inflammatory disorders. Sitagliptin is an inhibitor of dipeptidyl peptidase-4 (DPP4, also known as CD26), which is clinically used for DM treatment. However, the mechanism of sitagliptin’s efficiency in liver diseases is largely unknown. In this study, mice suffering from streptozotocin (STZ) exhibit elevated liver DPP4 expression and activity, as well as inflammatory and chronic liver injury phenotype, whereas specifically inhibiting the activity of DPP4 in mouse liver tissues and hepatocytes by sitagliptin contributes to decreased cytokines, oxidative stress, cell apoptosis, and inflammation in STZ-induced diabetic mice. Moreover, sitagliptin reduced TNFα or LPS-induced cellular reactive oxygen species (ROS) level, cell apoptosis, and protein expression in the NFκB signaling pathway in HepG2 cells or primary mouse hepatocytes. Altogether, our study confirms that sitagliptin may protect liver tissue by alleviating ROS production and NFκB signaling activation, providing a putative mechanism for preventing the development of diabetic liver disease.
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影响因子：
8.1
作者：
Baumeier C;Schlüter L;Saussenthaler S;Laeger T;Rödiger M;Alaze SA;Fritsche L;Häring HU;Stefan N;Fritsche A;Schwenk RW;Schürmann A
通讯作者：
Schürmann A
影响因子：
7.7
作者：
Kim, Su-Jin;Nian, Cuilan;Doudet, Doris J.;McIntosh, Christopher H. S.
通讯作者：
McIntosh, Christopher H. S.
影响因子：
3.8
作者：
Balaban, Yasemin H.;Korkusuz, Petek;Tatar, Gonca
通讯作者：
Tatar, Gonca
影响因子：
4.7
作者：
Abdelsalam, Rania M.;Safar, Marwa M.
通讯作者：
Safar, Marwa M.
影响因子：
3.7
作者：
Hu, Xingyun;Liu, Shanying;Li, Yan
通讯作者：
Li, Yan