Gene deletion of γ-actin impairs insulin-stimulated skeletal muscle glucose uptake in growing mice but not in mature adult mice

Jonas Roland Knudsen, Agnete B Madsen, Zhencheng Li, Nicoline Resen Andersen, Peter Schjerling, Thomas Elbenhardt Jensen*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

3 Citationer (Scopus)
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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.

OriginalsprogEngelsk
Artikelnummere15183
TidsskriftPhysiological Reports
Vol/bind10
Udgave nummer4
Antal sider11
ISSN2051-817X
DOI
StatusUdgivet - 2022

Bibliografisk note

CURIS 2022 NEXS 058
© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Emneord

  • Det Natur- og Biovidenskabelige Fakultet

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