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Updated: Nov 30, 2025

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
Published on: May 16, 2021
Vav2 catalysis-dependent pathways contribute to skeletal muscle growth and metabolic homeostasis
Sonia Rodríguez-Fdez1,2,3, L Francisco Lorenzo-Martín1,2,3, Isabel Fernández-Pisonero1,2,3
1Centro de Investigaación del Cáncer, CSIC-University of Salamanca, 37007, Salamanca, Spain.
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.
Insights
Skeletal muscle
Area of Science:
- Biochemistry
- Physiology
- Metabolism
Background:
- Skeletal muscle plays a crucial role in maintaining metabolic homeostasis.
- It regulates glucose uptake and facilitates interorgan communication.
- The insulin/IGF1 signaling pathway is central to muscle function and metabolism.
Purpose of the Study:
- To investigate the role of Vav2's catalytic activity in modulating insulin/IGF1 signaling in skeletal muscle.
- To understand how Vav2 impacts muscle mass, insulin sensitivity, and metabolic health.
Main Methods:
- Utilized mouse models with altered Vav2 catalytic activity (hypoactive and hyperactive).
- Assessed muscle mass, insulin responsiveness, and metabolic syndrome phenotypes.
- Examined the effects of high-fat diet-induced metabolic imbalance.
Main Results:
- Decreased Vav2 catalytic activity led to reduced muscle mass and insulin resistance.
- Increased Vav2 catalytic activity resulted in muscle hypertrophy and enhanced insulin sensitivity.
- Hypoactive Vav2 predisposed to metabolic imbalance, while hyperactive Vav2 protected against it.
Conclusions:
- Vav2's catalytic activity is a key regulator of insulin/IGF1 signaling output in skeletal muscle.
- Modulating Vav2 activity impacts muscle mass, insulin sensitivity, and overall metabolic health.
- Vav2 represents a novel regulatory layer in insulin family factor signaling within muscle tissue.
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