Lack of O-G1cNAcylation enhances exercise-dependent glucose utilization potentially through AMP -activated protein kinase activation in skeletal muscle
- Authors
- Murata, Koichiro; Morino, Katsutaro; Ida, Shogo; Ohashi, Natsuko; Lemecha, Mengistu; Park, Shi-Young; Ishikado, Atsushi; Kume, Shinji; Choi, Cheol Soo; Sekine, Osamu; Ugi, Satoshi; Maegawa, Hiroshi
- Issue Date
- 8-Jan-2018
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- O-GlcNAcylation; AMP-activated protein kinase; Skeletal muscle
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.495, no.2, pp.2098 - 2104
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 495
- Number
- 2
- Start Page
- 2098
- End Page
- 2104
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/4140
- DOI
- 10.1016/j.bbrc.2017.12.081
- ISSN
- 0006-291X
- Abstract
- O-G1cNAcylation is a post-translational modification that is characterized by the addition of N-acetylglucosamine (GIcNAc) to proteins by O-G1cNAc transferase (Ogt). The degree of O-GIcNAcylation is thought to be associated with glucotoxicity and diabetic complications, because GlcNAc is produced by a branch of the glycolytic pathway. However, its role in skeletal muscle has not been fully elucidated. In this study, we created skeletal muscle-specific Ogt knockout (Ogt-MKO) mice and analyzed their glucose metabolism. During an intraperitoneal glucose tolerance test, blood glucose was slightly lower in OgtMKO mice than in control Ogt-fiox mice. High fat diet-induced obesity and insulin resistance were reversed in Ogt-MKO mice. In addition, 12-month-old Ogt-MKO mice had lower adipose and body mass. A single bout of exercise significantly reduced blood glucose in Ogt-MKO mice, probably because of higher AMP-activated protein kinase cc (AMPKa) protein expression. Furthermore, intraperitoneal injection of 5-aminoimidazole-4-carboxamide ribonucleotide, an AMPK activator, resulted in a more marked decrease in blood glucose levels in Ogt-MKO mice than in controls. Finally, Ogt knockdown by siRNA in C2C12 myotubes significantly increased protein expression of AMPKa, glucose uptake and oxidation. In conclusion, loss of O-G1cNAcylation facilitates glucose utilization in skeletal muscle, potentially through AMPK activation. The inhibition of O-G1cNAcylation in skeletal muscle may have an anti-diabetic effect, through an enhancement of glucose utilization during exercise. (C) 2017 Elsevier Inc. All rights reserved.
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