Laboratory of Applied Nutrition and Metabolism, School of Physical Education and Sports, University of São Paulo, Av. Prof. Mello Moraes, 65, São Paulo, SP, 05508-030, Brazil.
Amino Acids. 2012 May;42(5):1695-701. doi: 10.1007/s00726-011-0871-9. Epub 2011 Mar 5.
We aimed to investigate the possible role of creatine (CR) supplementation in counteracting dexamethasone-induced muscle wasting and insulin resistance in rats. Also, we examined whether CR intake would modulate molecular pathways involved in muscle remodeling and insulin signaling. Animals were randomly divided into four groups: (1) dexamethasone (DEX); (2) control pair-fed (CON-PF); (3) dexamethasone plus CR (DEX-CR); and (4) CR pair-fed (CR-PF). Dexamethasone (5 mg/kg/day) and CR (5 g/kg/day) were given via drinking water for 7 days. Plantaris and extensor digitorum longus (EDL) muscles were removed for analysis. Plantaris and EDL muscle mass were significantly reduced in the DEX-CR and DEX groups when compared with the CON-PF and CR-PF groups (P<0.05). Dexamethasone significantly decreased phospho-Ser473-Akt protein levels compared to the CON-PF group (P<0.05) and CR supplementation aggravated this response (P<0.001). Serum glucose was significantly increased in the DEX group when compared with the CON-PF group (DEX 7.8±0.6 vs. CON-PF 5.2±0.5 mmol/l; P<0.05). CR supplementation significantly exacerbated hyperglycemia in the dexamethasone-treated animals (DEX-CR 15.1±2.4 mmol/l; P<0.05 vs. others). Dexamethasone reduced GLUT-4 translocation when compared with the CON-PF and CR-PF (P<0.05) groups and this response was aggravated by CR supplementation (P<0.05 vs. others). In conclusion, supplementation with CR resulted in increased insulin resistance and did not attenuate muscle wasting in rats treated with dexamethasone. Given the contrast with the results of human studies that have shown benefits of CR supplementation on muscle atrophy and insulin sensitivity, we suggest caution when extrapolating this animal data to human subjects.
我们旨在研究肌酸（CR）补充在对抗大鼠地塞米松诱导的肌肉减少和胰岛素抵抗中的可能作用。此外，我们还研究了 CR 摄入是否会调节参与肌肉重塑和胰岛素信号的分子途径。动物被随机分为四组：（1）地塞米松（DEX）；（2）对照限食（CON-PF）；（3）地塞米松加 CR（DEX-CR）；和（4）CR 限食（CR-PF）。通过饮用水给予地塞米松（5mg/kg/天）和 CR（5g/kg/天），共 7 天。取出比目鱼肌和伸趾长肌（EDL）进行分析。与 CON-PF 和 CR-PF 组相比，DEX-CR 和 DEX 组的比目鱼肌和 EDL 肌肉质量显著减少（P<0.05）。与 CON-PF 组相比，地塞米松显著降低磷酸化 Ser473-Akt 蛋白水平（P<0.05），而 CR 补充加重了这种反应（P<0.001）。与 CON-PF 组相比，DEX 组血清葡萄糖显著升高（DEX 7.8±0.6 与 CON-PF 5.2±0.5mmol/l；P<0.05）。CR 补充显著加重了地塞米松处理动物的高血糖（DEX-CR 15.1±2.4mmol/l；P<0.05 与其他组相比）。与 CON-PF 和 CR-PF 组相比，地塞米松降低了 GLUT-4 易位（P<0.05），而 CR 补充加重了这种反应（P<0.05 与其他组相比）。总之，CR 补充导致胰岛素抵抗增加，并且不能减轻地塞米松治疗大鼠的肌肉减少。鉴于与人类研究结果的对比，这些研究表明 CR 补充对肌肉萎缩和胰岛素敏感性有益，因此当将这些动物数据外推至人类受试者时，建议谨慎。
