Prothymosin-α overexpression contributes to the development of insulin resistance

Yu Chu Su, Horng Yih Ou, Hung Tsung Wu, Pensee Wu, Yi Cheng Chen, Bing Hua Su, Ai Li Shiau, Chih Jen Chang, Chao Liang Wu

研究成果: Article同行評審

12 引文 斯高帕斯(Scopus)


Context: Prothymosin-α (ProT) is involved in oxidative stress, inflammation, cell proliferation, and apoptosis. Increased oxidative stress and chronic inflammation participate in the pathogenesis of diabetes.Arecent study found that ProT is a ligand of toll-like receptor 4, which plays an important role in the development of insulin resistance. However, its physiological role remains poorly understood. Objective: The objective was to investigate whether ProT contributes to the development of insulin resistance. Design, Settings, and Patients: A total of 185 subjects were recruited and classified into nondiabetes (n=95) and newly diagnosed diabetes (n=90) groups. Transgenic mice overexpressing ProT were used to investigate the role of ProT in the development of insulin resistance. Lentiviral vectors carrying short hairpin RNA specific for ProT were delivered via the portal vein to silence hepatic ProT expression in mice with high-fat diet-induced insulin resistance. Glucose uptake was determined in L6 myotubes. Results: We show that the serum ProT levels of patients with type 2 diabetes were significantly higher than those of normal individuals (mean ± SEM, 419.8 ± 46.47 vs 246.4 ± 27.89 pg/mL; P < .001). Furthermore, ProT transgenic mice exhibited an insulin-resistant phenotype, whereas the silencing of hepatic ProT expression ameliorated high-fat diet-induced insulin resistance in C57BL/6 mice. In vitro studies reveal that ProT induced insulin resistance through a toll-like receptor 4-nuclear factor-κB-dependent pathway. Conclusions: Our results support the role for ProT in the development of insulin resistance. Therefore, ProT is a potential novel therapeutic target for type 2 diabetes.

頁(從 - 到)4114-4123
期刊Journal of Clinical Endocrinology and Metabolism
出版狀態Published - 2015 11月

All Science Journal Classification (ASJC) codes

  • 內分泌學、糖尿病和代謝
  • 生物化學
  • 內分泌
  • 臨床生物化學
  • 生物化學(醫學)


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