Endurance exercise training-responsive miR-19b-3p improves skeletal muscle glucose metabolism

Nat Commun. 2021 Oct 12;12(1):5948. doi: 10.1038/s41467-021-26095-0.


Skeletal muscle is a highly adaptable tissue and remodels in response to exercise training. Using short RNA sequencing, we determine the miRNA profile of skeletal muscle from healthy male volunteers before and after a 14-day aerobic exercise training regime. Among the exercise training-responsive miRNAs identified, miR-19b-3p was selected for further validation. Overexpression of miR-19b-3p in human skeletal muscle cells increases insulin signaling, glucose uptake, and maximal oxygen consumption, recapitulating the adaptive response to aerobic exercise training. Overexpression of miR-19b-3p in mouse flexor digitorum brevis muscle enhances contraction-induced glucose uptake, indicating that miR-19b-3p exerts control on exercise training-induced adaptations in skeletal muscle. Potential targets of miR-19b-3p that are reduced after aerobic exercise training include KIF13A, MAPK6, RNF11, and VPS37A. Amongst these, RNF11 silencing potentiates glucose uptake in human skeletal muscle cells. Collectively, we identify miR-19b-3p as an aerobic exercise training-induced miRNA that regulates skeletal muscle glucose metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • Energy Metabolism / genetics
  • Exercise / physiology*
  • Glucose / metabolism*
  • Healthy Volunteers
  • Humans
  • Kinesins / genetics
  • Kinesins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mitogen-Activated Protein Kinase 6 / genetics
  • Mitogen-Activated Protein Kinase 6 / metabolism
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Oxygen Consumption / genetics
  • Phosphorylation
  • Physical Conditioning, Animal
  • Protein Processing, Post-Translational*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction


  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • KIF13A protein, human
  • KIF13A-RET fusion protein, human
  • MIRN19 microRNA, human
  • MIRN19 microRNA, mouse
  • MicroRNAs
  • Oncogene Proteins, Fusion
  • RNA, Small Interfering
  • RNF11 protein, human
  • VPS37A protein, human
  • Mitogen-Activated Protein Kinase 6
  • Kinesins
  • Glucose