Gene deletion of γ-actin impairs insulin-stimulated skeletal muscle glucose uptake in growing mice but not in mature adult mice.
Jonas R KnudsenAgnete B MadsenZhencheng LiNicoline R AndersenPeter SchjerlingThomas Elbenhardt JensenPublished in: Physiological reports (2022)
The cortical cytoskeleton, consisting of the cytoplasmic actin isoforms β and/or γ-actin, has been implicated in insulin-stimulated GLUT4 translocation and glucose uptake in muscle and adipose cell culture. Furthermore, transgenic inhibition of multiple actin-regulating proteins in muscle inhibits insulin-stimulated muscle glucose uptake. The current study tested if γ-actin was required for insulin-stimulated glucose uptake in mouse skeletal muscle. Based on our previously reported age-dependent phenotype in muscle-specific β-actin gene deletion ( -/- ) mice, we included cohorts of growing 8-14 weeks old and mature 18-32 weeks old muscle-specific γ-actin -/- mice or wild-type littermates. In growing mice, insulin significantly increased the glucose uptake in slow-twitch oxidative soleus and fast-twitch glycolytic EDL muscles from wild-type mice, but not γ-actin -/- . In relative values, the maximal insulin-stimulated glucose uptake was reduced by ~50% in soleus and by ~70% in EDL muscles from growing γ-actin -/- mice compared to growing wild-type mice. In contrast, the insulin-stimulated glucose uptake responses in mature adult γ-actin -/- soleus and EDL muscles were indistinguishable from the responses in wild-type muscles. Mature adult insulin-stimulated phosphorylations on Akt, p70S6K, and ULK1 were not significantly affected by genotype. Hence, insulin-stimulated muscle glucose uptake shows an age-dependent impairment in young growing but not in fully grown γ-actin -/- mice, bearing phenotypic resemblance to β-actin -/- mice. Overall, γ-actin does not appear required for insulin-stimulated muscle glucose uptake in adulthood. Furthermore, our data emphasize the need to consider the rapid growth of young mice as a potential confounder in transgenic mouse phenotyping studies.
Keyphrases
- wild type
- skeletal muscle
- type diabetes
- high fat diet induced
- blood glucose
- cell migration
- glycemic control
- insulin resistance
- machine learning
- blood pressure
- cell proliferation
- transcription factor
- high throughput
- risk assessment
- big data
- resistance training
- middle aged
- artificial intelligence
- human health
- early life