Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Acta Physiol (Oxf). 2009 Nov;197(3):207-15. doi: 10.1111/j.1748-1716.2009.02010.x. Epub 2009 Jun 6.
In vivo whole body differences in glucose/lipid metabolism exist between men and women. Thus, we tested the hypothesis that intrinsic sex differences exist in skeletal muscle gene expression and glucose/lipid metabolism using cultured myotubes.
Myotube cultures were prepared for gene expression and metabolic studies from vastus lateralis skeletal muscle biopsies obtained from age-matched men (n = 11; 59 +/- 2 years) and post-menopausal women (n = 10; 60 +/- 1 years).
mRNA expression of several genes involved in glucose and lipid metabolism was higher in skeletal muscle biopsies from female vs. male donors, but unaltered between the sexes in cultured myotubes. Basal and insulin-stimulated glucose uptake, as well as glucose incorporation into glycogen, was similar in myotube cultures derived from male vs. female donors. In males vs. females, insulin increased glucose uptake (1.3 +/- 0.1 vs. 1.5 +/- 0.1-fold respectively) and incorporation into glycogen (2.3 +/- 0.3 vs. 2.0 +/- 0.3-fold respectively) to the same extent. Basal fatty acid oxidation and rate of uptake/accumulation was similar between sexes. In response to the 5'AMP-activated protein kinase activator AICAR, lipid oxidation was increased to the same extent in myotubes established from male vs. female donors (1.6 +/- 0.6 vs. 2.0 +/- 0.3-fold respectively). Moreover, the AICAR-induced rate of uptake/accumulation was similar between sexes.
Differences in metabolic parameters and gene expression profiles between age-matched men and post-menopausal women noted in vivo are not observed in cultured human skeletal muscle cells. Thus, the sexual dimorphism in glucose and lipid metabolism is likely a consequence of systemic whole body factors, rather than intrinsic differences in the skeletal muscle proper.
男性和女性体内的葡萄糖/脂质代谢存在整体差异。因此,我们通过培养的肌管来验证内在的性别差异是否存在于骨骼肌基因表达和葡萄糖/脂质代谢中的假设。
从年龄匹配的男性(n=11;59±2 岁)和绝经后女性(n=10;60±1 岁)的股外侧骨骼肌活检中制备肌管用于基因表达和代谢研究。
与男性供体相比,女性骨骼肌活检中涉及葡萄糖和脂质代谢的几种基因的 mRNA 表达更高,但在培养的肌管中男女之间没有差异。肌管培养物中的基础和胰岛素刺激的葡萄糖摄取以及葡萄糖掺入糖原的情况在男性和女性供体之间相似。与女性相比,男性的胰岛素增加了葡萄糖摄取(分别为 1.3±0.1 倍和 1.5±0.1 倍)和掺入糖原(分别为 2.3±0.3 倍和 2.0±0.3 倍)的程度相同。基础脂肪酸氧化和摄取/积累率在两性之间相似。在对 5'AMP 激活蛋白激酶激动剂 AICAR 的反应中,从男性和女性供体建立的肌管中脂类氧化增加到相同程度(分别为 1.6±0.6 倍和 2.0±0.3 倍)。此外,AICAR 诱导的摄取/积累率在两性之间相似。
在体内观察到的年龄匹配的男性和绝经后女性之间的代谢参数和基因表达谱差异在培养的人骨骼肌细胞中没有观察到。因此,葡萄糖和脂质代谢的性别二态性可能是全身整体因素的结果,而不是骨骼肌本身的内在差异。