Autor: |
Jonas R. Knudsen, Agnete B. Madsen, Zhencheng Li, Nicoline R. Andersen, Peter Schjerling, Thomas E. Jensen |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
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Zdroj: |
Physiological Reports, Vol 10, Iss 4, Pp n/a-n/a (2022) |
Druh dokumentu: |
article |
ISSN: |
2051-817X |
DOI: |
10.14814/phy2.15183 |
Popis: |
Abstract 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. |
Databáze: |
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