Helicobacter pylori infection causes hepatic insulin resistance by the c-Jun/miR-203/SOCS3 signaling pathway

被引:54
作者
Zhou, Xiaoying [1 ]
Liu, Wei [2 ]
Gu, Min [3 ]
Zhou, Hongwen [4 ]
Zhang, Guoxin [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanjing 210029, Jiangsu, Peoples R China
[2] First Peoples Hosp Suqian, Dept Gastroenterol, Suqian, Jiangsu, Peoples R China
[3] Changzhou Childrens Hosp, Dept Pediat, Changzhou, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Affiliated Hosp 1, Dept Endocrinol, Nanjing 210029, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Helicobacter pylori; Insulin resistance; miR-203; Suppressor of cytokine signaling 3; METABOLIC SYNDROME; SKELETAL-MUSCLE; ASSOCIATION; RECEPTOR; ACTIVATION; MICRORNAS; OBESITY; SOCS-3; PHOSPHORYLATION; INFLAMMATION;
D O I
10.1007/s00535-015-1051-6
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Epidemiological studies have indicated that patients with chronic Helicobacter pylori infection have an increased risk of developing type 2 diabetes mellitus, but the underlying mechanisms remain largely unknown. This study aimed to investigate whether H. pylori infection contributes to the development of insulin resistance, as well as the underlying mechanisms both in vivo and in vitro. The effect of H. pylori infection on glucose metabolism was evaluated in humans and mouse models. The role of the c-Jun/miR-203/suppressor of cytokine signaling 3 (SOCS3) pathway in H. pylori-induced insulin resistance was determined in vitro and was validated in vivo. Average fasting glucose levels were increased in patients (P = 0.012) and mice (P = 0.004) with H. pylori infection. Diabetic mice with H. pylori infection showed impaired glucose metabolism and insulin tolerance and hyperinsulinemia. Furthermore, H. pylori infection impaired insulin signaling in primary hepatocytes. H. pylori infection could upregulate SOCS3, a well-known insulin signaling inhibitor, by downregulating miR-203. SOCS3 overexpression interfered with insulin signaling proteins, and knockdown of SOCS3 alleviated H. pylori-induced impairment of insulin signaling. The transcription factor c-Jun, which affects gene expression, was induced by H. pylori infection and suppressed miR-203 expression. Our results demonstrated that H. pylori infection induced hepatic insulin resistance by the c-Jun/miR-203/SOCS3 signaling pathway and provide possible implications with regard to resolving insulin resistance.
引用
收藏
页码:1027 / 1040
页数:14
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