Activation of the hypoxia-inducible factor pathway by roxadustat improves glucose metabolism in human primary myotubes from men
Authors' conclusion
Roxadustat increases glycolysis and inhibits mitochondrial respiration in primary human myotubes regardless of diabetes status. Roxadustat may also improve insulin action on glycogen synthesis in myotubes from donors with type 2 diabetes.
Study context
- Population
- Primary skeletal muscle cell cultures from vastus lateralis biopsies of men with normal glucose tolerance (NGT) or T2D
- Participants
- 5 vs 8
- Comparison
- Roxadustat vs no roxadustat in myotubes from men with NGT or T2D
- NGTn = 5reference
- T2Dn = 8
- Outcome
- Effects of roxadustat on myotube metabolism
Methodological detailsin vitro, primary human myotubes
- In vitro
- Primary human myotubes
Main finding
As reported in the abstract
- Glycolytic rate increase with roxadustat, NGT
- 1.4-fold (p=0.0370)
- Glycolytic rate increase with roxadustat, T2D
- 1.7-fold (p=0.0044)
- Reduction in basal mitochondrial respiration with roxadustat in both groups
- p<0.01
- Insulin-stimulated glucose uptake enhanced by roxadustat, NGT (vs insulin only)
- 1.4-fold (p=0.0023)
- Roxadustat pretreatment enhanced insulin-stimulated glycogen synthesis, T2D
- p=0.0345
Further findings
Basal glucose uptake · similar
P = 0.4205
Basal glucose incorporation into glycogen · lower with NGT
P = 0.0344
Insulin-stimulated glycogen synthesis (insulin alone)
- Increase with insulin, NGT
- 1.9-fold (p=0.0025)
- Increase with insulin, T2D
- 1.7-fold (p=0.0031)
Original publication
Activation of the hypoxia-inducible factor pathway by roxadustat improves glucose metabolism in human primary myotubes from men. Diabetologia. Published 30 May 2024. doi:10. 1007/ s00125-024-06185-6
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