Unknown

Dataset Information

0

Vav2 catalysis-dependent pathways contribute to skeletal muscle growth and metabolic homeostasis.


ABSTRACT: Skeletal muscle promotes metabolic balance by regulating glucose uptake and the stimulation of multiple interorgan crosstalk. We show here that the catalytic activity of Vav2, a Rho GTPase activator, modulates the signaling output of the IGF1- and insulin-stimulated phosphatidylinositol 3-kinase pathway in that tissue. Consistent with this, mice bearing a Vav2 protein with decreased catalytic activity exhibit reduced muscle mass, lack of proper insulin responsiveness and, at much later times, a metabolic syndrome-like condition. Conversely, mice expressing a catalytically hyperactive Vav2 develop muscle hypertrophy and increased insulin responsiveness. Of note, while hypoactive Vav2 predisposes to, hyperactive Vav2 protects against high fat diet-induced metabolic imbalance. These data unveil a regulatory layer affecting the signaling output of insulin family factors in muscle.

SUBMITTER: Rodriguez-Fdez S 

PROVIDER: S-EPMC7669868 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC8358859 | biostudies-literature
| S-EPMC5437870 | biostudies-literature
| S-EPMC5741141 | biostudies-literature
| S-EPMC4762428 | biostudies-literature
| S-EPMC3322465 | biostudies-literature
| S-EPMC3868675 | biostudies-literature
| S-EPMC6289786 | biostudies-literature
| S-EPMC7749575 | biostudies-literature
| S-EPMC4390264 | biostudies-literature
| S-EPMC4530624 | biostudies-literature