Voluntary exercise can ameliorate insulin resistance by reducing iNOS-mediated S-nitrosylation of Akt in the liver in obese rats

Takamasa Tsuzuki, Shohei Shinozaki, Hideko Nakamoto, Masao Kaneki, S. Goto, Kentaro Shimokado, Hiroyuki Kobayashi, Hisashi Naito, Zane Andrews

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
JournalPLoS One
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 14 2015

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Inbred OLETF Rats
Nitric Oxide Synthase Type II
insulin resistance
Liver
Insulin Resistance
Rats
exercise
Insulin
liver
rats
Metabolism
Glucose
Signal transduction
Molecules
glucose
Medical problems
metabolism
Running
Type 2 Diabetes Mellitus
wheels

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Voluntary exercise can ameliorate insulin resistance by reducing iNOS-mediated S-nitrosylation of Akt in the liver in obese rats. / Tsuzuki, Takamasa; Shinozaki, Shohei; Nakamoto, Hideko; Kaneki, Masao; Goto, S.; Shimokado, Kentaro; Kobayashi, Hiroyuki; Naito, Hisashi; Andrews, Zane.

In: PLoS One, Vol. 10, No. 7, 14.07.2015.

Research output: Contribution to journalArticle

Tsuzuki, T, Shinozaki, S, Nakamoto, H, Kaneki, M, Goto, S, Shimokado, K, Kobayashi, H, Naito, H & Andrews, Z 2015, 'Voluntary exercise can ameliorate insulin resistance by reducing iNOS-mediated S-nitrosylation of Akt in the liver in obese rats', PLoS One, vol. 10, no. 7. https://doi.org/10.1371/journal.pone.0132029
Tsuzuki, Takamasa ; Shinozaki, Shohei ; Nakamoto, Hideko ; Kaneki, Masao ; Goto, S. ; Shimokado, Kentaro ; Kobayashi, Hiroyuki ; Naito, Hisashi ; Andrews, Zane. / Voluntary exercise can ameliorate insulin resistance by reducing iNOS-mediated S-nitrosylation of Akt in the liver in obese rats. In: PLoS One. 2015 ; Vol. 10, No. 7.
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