ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes.
ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes.
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ASK1 相互作用蛋白 1 作为 2 型糖尿病的新型预测因子
DOI：
10.3389/fendo.2022.896753
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发表时间：
2022
影响因子：
5.2
通讯作者：
He, Li
中科院分区：
文献类型：
--
作者：
Song, Zhigao;Chen, Cong;He, Jipei;Liu, Bixia;Ji, Weidong;Wu, Liangping;He, Li
2型糖尿病（Type 2 Diabetes，T2 D）是一种以肿瘤坏死因子（tumor necrosis factor，TNF）-α高分泌为特征的慢性炎症性疾病，但T2 D中TNF-α产生的调控途径尚未完全阐明。ASK 1相互作用蛋白1（AIP 1）是一种信号支架蛋白，可调节与炎症相关的几种途径。在这项研究中，我们的目的是研究AIP 1在T2 D发展中的作用。我们的研究结果显示，与肥胖患者相比，肥胖T2 D患者的网膜脂肪组织（OAT）中AIP 1表达下调。此外，Pearson相关性检验显示AIP 1与稳态模型评估的胰岛素抵抗（HOMA-IR，r = -0.4829）和腰臀比（r = -0.2614）呈负相关，这是T2 D的主要临床指标。如蛋白质组学分析、免疫组织化学和ELISA所揭示的，患有T2 D的肥胖患者的OAT和血清呈现高炎症状态。肥胖2型糖尿病患者血清中炎症因子TNF-α和C反应蛋白C（CRP）水平升高与HOMA-IR呈正相关（TNF-α，r = 0.4728; CRP，r = 0.5522）。有趣的是，脂肪细胞中AIP 1的缺乏促进了TNF-α的分泌并延缓了葡萄糖的摄取。从机制上讲，人类脂肪细胞中AIP 1的缺失激活了JNK、p38 MAPK和ERK 1/2信号转导。此外，使用特异性抑制剂抑制这些信号通路可以抑制这些信号激活和AIP 1缺陷引起的胰岛素抵抗。此外，腹腔镜Roux-en-Y胃旁路（RYGB）手术后，T2 D患者OAT中的AIP 1和TNF-α表达恢复至正常水平。这些结果表明，AIP 1与T2 D的临床指标呈负相关。它通过JNK、p38 MAPK和ERK 1/2信号转导调节OAT中TNF-α的表达。
Type 2 diabetes (T2D) mellitus is a chronic inflammatory disease characterized with high secretion of tumor necrosis factor (TNF)-α, but the regulatory pathway of TNF-α production in T2D has not been fully elucidated. ASK1-interacting protein 1 (AIP1) is a signaling scaffold protein that modulates several pathways associated with inflammation. In this study, we aimed to investigate the role of AIP1 in T2D development. Our results revealed that AIP1 was downregulated in omental adipose tissue (OAT) of obese patients with T2D compared with that in obese patients. In addition, Pearson’s correlation test showed that AIP1 was negatively correlated with the homeostatic model assessment for insulin resistance (HOMA-IR, r = -0.4829) and waist-to-hip ratio (r = -0.2614), which are major clinical indexes of T2D. As revealed by the proteomic analysis, immunohistochemistry, and ELISA, the OAT and the serum of obese patients with T2D presented high inflammatory status. And the increased inflammatory factors TNF-α and C-reactive protein C (CRP) in the serum of obese patients with T2D showed a positive correlation with HOMA-IR (TNF-α, r = 0.4728; CRP, r = 0.5522). Interestingly, AIP1 deficiency in adipocytes facilitated TNF-α secretion and retarded glucose uptake. Mechanistically, AIP1 deletion in human adipocytes activated JNK, p38 MAPK, and ERK1/2 signaling. Furthermore, inhibition of these signaling pathways using specific inhibitors could suppress these signal activation and insulin resistance caused by AIP1 deficiency. In addition, AIP1 and TNF-α expression in the OAT of patients with T2D recovered to normal levels after laparoscopic Roux-en-Y gastric bypass (RYGB) surgery. These findings indicate that AIP1 is negatively correlated with the clinical indexes of T2D. It modulates TNF-α expression in OAT via JNK, p38 MAPK, and ERK1/2 signaling.
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影响因子：
4
作者：
Muhammad SA;Raza W;Nguyen T;Bai B;Wu X;Chen J
通讯作者：
Chen J
影响因子：
14.9
作者：
Perez-Riverol Y;Bai J;Bandla C;García-Seisdedos D;Hewapathirana S;Kamatchinathan S;Kundu DJ;Prakash A;Frericks-Zipper A;Eisenacher M;Walzer M;Wang S;Brazma A;Vizcaíno JA
通讯作者：
Vizcaíno JA
影响因子：
9.3
作者：
Min W;Pober JS
通讯作者：
Pober JS
影响因子：
4.8
作者：
Zhang, HF;Zhang, R;Min, W
通讯作者：
Min, W
影响因子：
4.8
作者：
Li, XH;Zhang, R;Min, W
通讯作者：
Min, W