GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration
Scientific Reports · 2021
Raising glucose uptake in the newborn mouse heart improved its ability to regenerate after injury.
Research question
Does glucose metabolism regulate the regenerative capacity of the neonatal heart?
Clinical & scientific significance
Glucose metabolism appears to be a determinant of neonatal heart regeneration, likely through nucleotide supply — a lead for future heart-repair strategies (mouse data).
Key findings reported in the paper
- GLUT1 overexpression increased glucose uptake and glycogen storage in the postnatal heart.
- After cryoinjury, transgenic hearts regenerated better, with less fibrosis.
- A Tnnt2-low cardiomyocyte population showed higher mitotic activity with high intracellular glucose; glucose metabolites, including nucleotides, increased.
- Blocking nucleotide biosynthesis abolished the regenerative advantage.
Objectives
To test whether cardiac-specific GLUT1 overexpression changes regeneration after injury, and through which mechanism.
Methods
Transgenic mice overexpressing Glut1 in the heart; cryoinjury; flow cytometry of cardiomyocytes; metabolic profiling; inhibition of nucleotide biosynthesis.
This summary is based only on the published abstract.
Glucose and the regenerating newborn heart
01
Before birth
The heart relies mainly on glucose.
02
After birth
Fuel switches to fatty acids as regenerative capacity is lost.
03
More GLUT1
Extra glucose transporter raises glucose uptake and glycogen storage.
04
Nucleotide supply
Glucose metabolites fuel dividing heart-muscle cells.
05
Better repair
Greater regeneration with less scarring after injury.
Studying glucose metabolism to inform therapies for heart failure | Viviana Fajardo, M.D.
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Authors
Fajardo VM, Feng I, Chen BY, Perez-Ramirez CA, Shi B, Clark P, Tian R, Lien CL, Pellegrini M, Christofk H, Nakano H, Nakano A
Citation
GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration. Sci Rep. 2021; 11(1):8669. doi:10.1038/s41598-021-88159-x. PMID: 33883682.
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