title: Voluntary Exercise Can Ameliorate Insulin Resistance by Reducing iNOS-Mediated S-Nitrosylation of Akt in the Liver in Obese Rats.
abstract: Voluntary exercise can ameliorate insulin resistance. The underlying mechanism, however, remains to be elucidated. We previously demonstrated that inducible nitric oxide synthase (iNOS) in the liver plays an important role in hepatic insulin resistance in the setting of obesity. In this study, we tried to verify our hypothesis that voluntary exercise improves insulin resistance by reducing the expression of iNOS and subsequent S-nitrosylation of key molecules of glucose metabolism in the liver. Twenty-one Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus, and 18 non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats were randomly assigned to a sedentary group or exercise group subjected to voluntary wheel running for 20 weeks. The voluntary exercise significantly reduced the fasting blood glucose and HOMA-IR in the OLETF rats. In addition, the exercise decreased the amount of iNOS mRNA in the liver in the OLETF rats. Moreover, exercise reduced the levels of S-nitrosylated Akt in the liver, which were increased in the OLETF rats, to those observed in the LETO rats. These findings support our hypothesis that voluntary exercise improves insulin resistance, at least partly, by suppressing the iNOS expression and subsequent S-nitrosylation of Akt, a key molecule of the signal transduction pathways in glucose metabolism in the liver.
authors.affiliation: Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan; Research Fellow of Japan Society for promotion of Science, Tokyo, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Tsuzuki
authors.affiliation: Department of Arteriosclerosis and Vascular Biology, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Shinozaki
authors.affiliation: Institute of Health and Sports Science & Medicine, Juntendo University Graduate School of Health and Sports Science, Chiba, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Nakamoto
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Masao
authors.initials: M
authors.lastname: Kaneki
authors.affiliation: Institute of Health and Sports Science & Medicine, Juntendo University Graduate School of Health and Sports Science, Chiba, Japan.
authors.forename: Sataro
authors.initials: S
authors.lastname: Goto
authors.affiliation: Department of Geriatrics and Vascular Medicine, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shimokado
authors.affiliation: Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan; Department of General Medicine, Mito Medical Center, Tsukuba University Hospital, Ibaraki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Naito
mesh_terms: D000818:Animals; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009765:Obesity / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D014280:Triglycerides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases