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Decreased Muscle‐derived Musclin by Chronic Resistance Exercise is Associated with Improved Insulin Resistance in Rats with Type 2 Diabetes
Author(s) -
Shimomura Mio,
Horii Naoki,
Fujie Shumpei,
Inoue Kenichiro,
Hasegawa Natsuki,
Iemitsu Keiko,
Uchida Masataka,
Iemitsu Motoyuki
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.05350
Subject(s) - medicine , endocrinology , insulin resistance , skeletal muscle , protein kinase b , type 2 diabetes , glucose transporter , diabetes mellitus , downregulation and upregulation , insulin , signal transduction , chemistry , biochemistry , gene
Chronic resistance exercise induces improved hyperglycemia in patients with type 2 diabetes mellitus. Musclin, a muscle‐derived secretory factor, is involved in the induction of insulin resistance via the downregulation of the glucose transporter‐4 (GLUT‐4) signaling pathway in skeletal muscles. However, whether musclin affects the mechanism of resistance exercise remains unclear. This study aimed to test the hypothesis that decreased muscle‐derived musclin secretion in chronic resistance exercise is involved in improvement of insulin resistance via the GLUT‐4 signaling pathway in rats with type 2 diabetes. Methods Male, 20‐week‐old, Otsuka Long‐Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model, were randomly divided into two groups: sedentary control (OLETF‐Con) and chronic resistance exercise (OLETF‐RT; climbing a ladder three times a week on alternate days for 8 weeks), whereas Long‐Evans Tokushima Otsuka (LETO) rats were used as the nondiabetic sedentary control group. Results OLETF‐Con rats showed increased fasting glucose levels, decreased insulin sensitivity index (QUICKI), muscle GLUT‐4 translocation, and protein kinase B (Akt) phosphorylation, and concomitantly increased muscle musclin expression as compared with LETO rats (P < 0.01). In contrast, OLETF‐RT rats significantly reduced muscle musclin expression, improved fasting glucose levels, and QUICKI through an accelerated muscle GLUT‐4/Akt signaling pathway as compared with OLETF‐Con rats (P < 0.01). Moreover, musclin protein levels in skeletal muscle were positively correlated with fasting blood glucose (r = 0.717, P < 0.01), and negatively correlated with QUICKI (r = ‐0.491, P < 0.05), muscle Akt phosphorylation (r = ‐0.475, P < 0.05), and GLUT‐4 translocation levels (r = ‐0.643, P < 0.01). Conclusions These findings suggest that the reduction in muscle‐derived musclin production by chronic resistance exercise may be involved in improved insulin resistance in rats with type 2 diabetes.