Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake—via AMP-activated protein kinase (AMPK)—after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of β-myosin heavy chain (β-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated β-mhc, Hk2 and Pfk2 mRNA levels. These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

中文翻译：

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睾丸激素通过AMPK和雄激素信号激活心肌肥大中的葡萄糖代谢

睾丸激素调节营养和能量平衡，以维持心肌细胞中蛋白质的合成和代谢，但是超生理学浓度会引起心肌肥大。以前，我们确定在心肌细胞进行急性治疗后，睾丸激素可通过AMP激活的蛋白激酶（AMPK）增加葡萄糖的摄取。然而，葡萄糖摄取的长高是否参与了葡萄糖代谢的长期变化，还是心肌细胞生长过程中是否需要葡萄糖摄取仍然未知。在这项研究中，我们假设睾丸激素处理过的心肌细胞通过AMPK和雄激素受体（AR）吸收葡萄糖和糖酵解增加。用100 nM睾丸激素刺激培养的心肌细胞24小时，并通过增加β-肌球蛋白重链（β-mhc）的细胞大小和mRNA水平来证实肥大。通过2-NBDG评估葡萄糖摄取。糖酵解和糖酵解能力通过测量细胞外酸化率（ECAR）来确定。睾丸激素诱导的心肌肥大，伴有葡萄糖摄取增加，糖酵解增强和己糖激酶2的mRNA表达上调。此外，睾丸激素增加了AMPK磷酸化（Thr172），而对AMPK和AR的抑制均阻止了由睾丸激素诱导的糖酵解和心肌肥大。此外，成年雄性大鼠在第5周补充睾丸激素会诱发心脏肥大，并上调β-mhc，Hk2和Pfk2 mRNA水平。这些结果表明，睾丸激素通过激活AMPK和AR信号传导来刺激葡萄糖代谢，这对于诱导心肌细胞肥大至关重要。