Type 2 & other diabetes

Activation of the hypoxia-inducible factor pathway by roxadustat improves glucose metabolism in human primary myotubes from men

DiabetologiaPublished Mechanistic study

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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