Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
Department of Orthopedic Surgery M, Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark.
Physiol Rep. 2022 Feb;10(4):e15183. doi: 10.14814/phy2.15183.
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.
皮质细胞骨架由细胞质肌动蛋白同种型β和/或γ-肌动蛋白组成，它与胰岛素刺激的 GLUT4 易位和肌肉及脂肪细胞培养中的葡萄糖摄取有关。此外，肌肉中多种肌动蛋白调节蛋白的转基因抑制会抑制胰岛素刺激的肌肉葡萄糖摄取。本研究检测了γ-肌动蛋白是否是小鼠骨骼肌胰岛素刺激的葡萄糖摄取所必需的。基于我们之前报道的肌肉特异性β-肌动蛋白基因缺失（）小鼠的年龄依赖性表型，我们纳入了生长中 8-14 周龄和成熟 18-32 周龄的肌肉特异性γ-肌动蛋白小鼠或野生型同窝仔鼠的队列。在生长中的小鼠中，胰岛素显著增加了野生型小鼠慢收缩氧化比目鱼肌和快收缩糖酵解 ED 肌肉的葡萄糖摄取，但不是γ-肌动蛋白。在相对值中，与生长中的野生型小鼠相比，生长中的γ-肌动蛋白小鼠比目鱼肌和 ED 肌肉中最大的胰岛素刺激葡萄糖摄取减少了约 50%和约 70%。相比之下，成熟的成年γ-肌动蛋白比目鱼肌和 ED 肌肉的胰岛素刺激葡萄糖摄取反应与野生型肌肉的反应无法区分。成熟的成年胰岛素刺激的 Akt、p70S6K 和 ULK1 磷酸化不受基因型的显著影响。因此，年轻生长中的胰岛素刺激的肌肉葡萄糖摄取出现年龄依赖性损伤，但在完全生长的γ-肌动蛋白小鼠中没有，其表型与β-肌动蛋白小鼠相似。总的来说，γ-肌动蛋白在成年期似乎不是胰岛素刺激的肌肉葡萄糖摄取所必需的。此外，我们的数据强调了在转基因小鼠表型研究中需要考虑年轻小鼠的快速生长作为一个潜在的混杂因素。
