Decreased muscle-derived musclin by chronic resistance exercise is associated with improved insulin resistance in rats with type 2 diabetes

Physiol Rep. 2021 May;9(9):e14823. doi: 10.14814/phy2.14823.


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 clarify whether decreased muscle-derived musclin secretion in chronic resistance exercise is involved in the improvement of insulin resistance via the GLUT-4 signaling pathway in rats with type 2 diabetes. 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 rats were used as the nondiabetic sedentary control group. 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. In contrast, OLETF-RT rats significantly reduced muscle musclin expression, improved hyperglycemia, and QUICKI through an accelerated muscle GLUT-4/Akt signaling pathway. Moreover, chronic resistance exercise-induced reduction of muscle musclin was correlated with changes in fasting glucose, QUICKI, GLUT-4 translocation, and Akt phosphorylation. 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.

Keywords: insulin resistance; musclin; resistance exercise; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Glucose Transporter Type 4 / metabolism
  • Insulin Resistance*
  • Male
  • Motor Activity*
  • Muscle, Skeletal / metabolism
  • Physical Conditioning, Animal / methods
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Signal Transduction
  • Transcription Factors / metabolism*


  • Glucose Transporter Type 4
  • Ostn protein, rat
  • Slc2a4 protein, rat
  • Transcription Factors
  • Proto-Oncogene Proteins c-akt