Skeletal muscle RUNX1 is related to insulin sensitivity through its effect on myogenic potential

in European Journal of Endocrinology
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  • 1 Department of Metabolic Diseases, Medical University of Białystok, Białystok, Poland
  • | 2 Department of Prophylaxis of Metabolic Diseases, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland
  • | 3 Department of Internal Medicine and Metabolic Diseases, Medical University of Białystok, Białystok, Poland

Correspondence should be addressed to M Karczewska-Kupczewska; Email: monika3101@wp.pl

*(M Stefanowicz and A Nikołajuk contributed equally to this work)

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Objective

Skeletal muscle is the major site of insulin action. There are limited data on the relationship between insulin action and skeletal muscle myogenic/regenerative potential. RUNX1 is a transcription factor which plays a role in muscle development and regeneration. The aim of our study was to assess the role of skeletal muscle myogenic/regenerative potential in the development of insulin resistance through the studies on RUNX1 transcription factor.

Design

This study is a cross-sectional study. Experimental part with myoblast cell line culture.

Methods

We examined 41 young healthy volunteers, 21 normal weight and 20 with overweight or obesity. Hyperinsulinemic-euglycemic clamp and vastus lateralis muscle biopsy were performed. In L6 myoblast and human skeletal muscle myoblasts (hSkMM) cell cultures, RUNX1 was silenced at two stages of development. Cell growth, the expression of markers of myogenesis, nuclei fusion index, Akt phosphorylation and glucose uptake were measured.

Results

Skeletal muscle RUNX1 expression was decreased in overweight/obese individuals in comparison with normal-weight individuals and was positively related to insulin sensitivity, independently of BMI. Runx1 loss-of-function at the stage of myoblast inhibited myoblast proliferation and differentiation and reduced insulin-stimulated Akt phosphorylation and insulin-stimulated glucose uptake. In contrast, Runx1 knockdown in myotubes did not affect Akt phosphorylation, glucose uptake and other parameters studied.

Conclusions

Myogenic/regenerative potential of adult skeletal muscle may be an important determinant of insulin action. Our data suggest that muscle RUNX1 may play a role in the modulation of insulin action through its effect on myogenesis.

Supplementary Materials

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
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