Gut microbe-derived extracellular vesicles induce insulin resistance, thereby impairing glucose metabolism in skeletal muscle

被引：173

作者：

Choi, Youngwoo ^{[1
]}

Kwon, Yonghoon ^{[1
]}

Kim, Dae-Kyum ^{[1
]}

Jeon, Jinseong ^{[1
]}

Jang, Su Chul ^{[1
]}

Wang, Taejun ^{[2
]}

Ban, Minjee ^{[1
]}

Kim, Min-Hye ^{[3
,4
]}

Jeon, Seong Gyu ^{[1
]}

Kim, Min-Sun ^{[5
]}

Choi, Cheol Soo ^{[6
,7
]}

Jee, Young-Koo ^{[8
]}

Gho, Yong Song ^{[1
]}

Ryu, Sung Ho ^{[1
]}

Kim, Yoon-Keun ^{[3
,4
]}

机构：

[1] Pohang Univ Sci & Technol POSTECH, Dept Life Sci, Pohang, South Korea

[2] POSTECH, Dept Interdisciplinary Biosci & Biotechnol, Pohang, South Korea

[3] Ewha Womans Univ, Dept Med, Sch Med, Seoul, South Korea

[4] Ewha Inst Convergence Med, Seoul, South Korea

[5] Univ Ulsan, Dept Internal Med, Coll Med, Seoul, South Korea

[6] Gachon Univ, Korea Mouse Metab Phenotyping Ctr, Lee Gil Ya Canc & Diabet Inst, Inchon, South Korea

[7] Gachon Univ, Div Endocrinol, Gil Med Ctr, Inchon, South Korea

[8] Dankook Univ, Dept Internal Med, Coll Med, Cheonan, South Korea

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

基金：

新加坡国家研究基金会;

关键词：

MEMBRANE-VESICLES; OBESITY; INFLAMMATION; ENDOTOXEMIA; DATABASE; RETICULOCYTES; TRANSFERRIN; MECHANISMS; RECEPTOR; EZTAXON;

D O I：

10.1038/srep15878

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Gut microbes might influence host metabolic homeostasis and contribute to the pathogenesis of type 2 diabetes (T2D), which is characterized by insulin resistance. Bacteria-derived extracellular vesicles (EVs) have been suggested to be important in the pathogenesis of diseases once believed to be noninfectious. Here, we hypothesize that gut microbe-derived EVs are important in the pathogenesis of T2D. In vivo administration of stool EVs from high fat diet (HFD)-fed mice induced insulin resistance and glucose intolerance compared to regular diet (RD)-fed mice. Metagenomic profiling of stool EVs by 16S ribosomal DNA sequencing revealed an increased amount of EVs derived from Pseudomonas panacis (phylum Proteobacteria) in HFD mice compared to RD mice. Interestingly, P. panacis EVs blocked the insulin signaling pathway in both skeletal muscle and adipose tissue. Moreover, isolated P. panacis EVs induced typical diabetic phenotypes, such as glucose intolerance after glucose administration or systemic insulin injection. Thus, gut microbe-derived EVs might be key players in the development of insulin resistance and impairment of glucose metabolism promoted by HFD.

引用

页数：11

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