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: 雜誌貢獻文章

4 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)4114-4123
頁數10
期刊Journal of Clinical Endocrinology and Metabolism
100
發行號11
DOIs
出版狀態已發佈 - 十一月 1 2015
對外發佈Yes

指紋

Insulin Resistance
Insulin
Medical problems
Toll-Like Receptor 4
High Fat Diet
Oxidative stress
Type 2 Diabetes Mellitus
Transgenic Mice
Nutrition
Oxidative Stress
Inflammation
Fats
Liver
Skeletal Muscle Fibers
Portal Vein
Inbred C57BL Mouse
Cell proliferation
Small Interfering RNA
Cell Proliferation
Apoptosis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

引用此文

Prothymosin-α overexpression contributes to the development of insulin resistance. / Su, Yu Chu; Ou, Horng Yih; Wu, Hung Tsung; Wu, Pensee; Chen, Yi Cheng; Su, Bing Hua; Shiau, Ai Li; Chang, Chih Jen; Wu, Chao Liang.

於: Journal of Clinical Endocrinology and Metabolism, 卷 100, 編號 11, 01.11.2015, p. 4114-4123.

研究成果: 雜誌貢獻文章

Su, Yu Chu ; Ou, Horng Yih ; Wu, Hung Tsung ; Wu, Pensee ; Chen, Yi Cheng ; Su, Bing Hua ; Shiau, Ai Li ; Chang, Chih Jen ; Wu, Chao Liang. / Prothymosin-α overexpression contributes to the development of insulin resistance. 於: Journal of Clinical Endocrinology and Metabolism. 2015 ; 卷 100, 編號 11. 頁 4114-4123.
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abstract = "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.",
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AU - Su, Yu Chu

AU - Ou, Horng Yih

AU - Wu, Hung Tsung

AU - Wu, Pensee

AU - Chen, Yi Cheng

AU - Su, Bing Hua

AU - Shiau, Ai Li

AU - Chang, Chih Jen

AU - Wu, Chao Liang

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N2 - 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.

AB - 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.

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