Author:
Zempo Hirofumi,Kim Su-Jeong,Fuku Noriyuki,Nishida Yuichiro,Higaki Yasuki,Wan Junxiang,Yen Kelvin,Miller Brendan,Vicinanza Roberto,Miyamoto-Mikami Eri,Kumagai Hiroshi,Naito Hisashi,Xiao Jialin,Mehta Hemal H.,Lee Changhan,Hara Megumi,Patel Yesha M.,Setiawan Veronica W.,Moore Timothy M.,Hevener Andrea L.,Sutoh Yoichi,Shimizu Atsushi,Kojima Kaname,Kinoshita Kengo,Tanaka Keitaro,Cohen Pinchas
Abstract
AbstractType 2 Diabetes (T2D) is an emerging public health problem in Asia. An Asian mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n=27,527, J-MICC, MEC, and TMM) showed that males but not females with the C-allele exhibit a higher prevalence of T2D. Furthermore, in J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitizationin vitro. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.
Publisher
Cold Spring Harbor Laboratory
Cited by
2 articles.
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