Gut microbe-derived extracellular vesicles induce insulin resistance, thereby impairing glucose metabolism in skeletal muscle.
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 non-infectious. 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.
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Youngwoo
Y
Choi
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Yonghoon
Y
Kwon
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Dae-Kyum
DK
Kim
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Jinseong
J
Jeon
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Su Chul
SC
Jang
Department of Interdisciplinary Biosciences and Biotechnology, POSTECH, Pohang, Republic of Korea.
Taejun
T
Wang
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Minjee
M
Ban
Department of Medicine, Ewha Womans University School of Medicine and Ewha Institute of Convergence Medicine, Seoul, Republic of Korea.
Min-Hye
MH
Kim
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Seong Gyu
SG
Jeon
Department of Internal Medicine, Ulsan University College of Medicine, Seoul, Republic of Korea.
Min-Sun
MS
Kim
Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, and Division of Endocrinology, Gil Medical Center, Gachon University, Incheon, Republic of Korea.
Cheol Soo
CS
Choi
Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea.
Young-Koo
YK
Jee
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Yong Song
YS
Gho
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Sung Ho
SH
Ryu
Department of Medicine, Ewha Womans University School of Medicine and Ewha Institute of Convergence Medicine, Seoul, Republic of Korea.
Yoon-Keun
YK
Kim
D000818:Animals; D000067128:Extracellular Vesicles / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D011549:Pseudomonas / Q000737:chemistry*
D005947:Glucose