title: Exercise training improves basal blood glucose metabolism with no changes of cytosolic inhibitor B kinase or c-Jun N-terminal kinase activation in skeletal muscle of Otsuka Long-Evans Tokushima fatty rats.
abstract: Redox-sensitive stress kinases and heat shock protein 72 (Hsp72) have been considered to be associated with the development of type 2 diabetes in skeletal muscle. However, the effect of exercise training on skeletal muscle of type 2 diabetic models is largely unknown. The purpose of this study was to investigate the effect of 12 weeks of exercise training on gastrocnemius of type 2 diabetic rats, by examining the activation of c-Jun N-terminal kinase (JNK), the nuclear factor B (NF-B) pathway and Hsp72. Total hydroperoxide and 4-hydroxynoneal, as oxidative stress markers, were also examined. Otsuka Long-Evans Tokushima fatty (OLEFT) rats were randomly divided into an exercise training group (Ex-OLETF, n = 8) and a sedentary group (Sed-OLETF, n = 8), while Long-Evans Tokushima Otsuka (LETO) rats were used as a control group (Con-LETO, n = 5). The Ex-OLETF rats were trained on a treadmill five times a week for 12 weeks. The levels of hydroperoxide and 4-hydroxynoneal in both Ex-OLETF and Sed-OLETF were significantly higher compared with Con-LETO, but there was no difference between Ex-OLETF and Sed-OLETF. Levels of inhibitor B kinase, JNK activation and p65 nuclear translocation followed a similar pattern to that observed in oxidative stress markers. The level of Hsp72 in Ex-OLETF was increased by exercise training, but it did not reach the level observed in Con-LETO. The NF-B DNA binding activity in Sed-OLETF was significantly higher compared with Con-LETO. Although it was not statistically significant, exercise training in Ex-OLETF showed a trend to reduce the activation of NF-B DNA binding activity compared with Sed-OLETF (P = 0.104). Our findings indicate that exercise training improves basal glucose metabolism without a change in stress kinases, and that nuclear regulation of NF-B activity in diabetic muscle could be regulated independently of the cytosolic pathway. Our study also suggests a possibility that exercise-induced Hsp72 serves as a protective mechanism in skeletal muscle of OLETF rats.
authors.affiliation: Health and Exercise Science Laboratory, Institute of Sports Science, Seoul National University, Gwanangno, Gwanak-gu, Seoul, Korea.
authors.forename: Hojun
authors.initials: H
authors.lastname: Lee
authors.forename: Hyukki
authors.initials: H
authors.lastname: Chang
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Si-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Kyung-Mook
authors.initials: KM
authors.lastname: Choi
authors.forename: Wook
authors.initials: W
authors.lastname: Song
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005951:Glucose Tolerance Test; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D020334:Rats, Inbred OLETF; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000447:Aldehydes; D001786:Blood Glucose; D050884:HSP72 Heat-Shock Proteins; D051996:Transcription Factor RelA; D006861:Hydrogen Peroxide; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; C027576:4-hydroxy-2-nonenal