Effects of activated vitamin D, alfacalcidol, and low-intensity aerobic exercise on osteopenia and muscle atrophy in type 2 diabetes mellitus model rats.
Effects of activated vitamin D, alfacalcidol, and low-intensity aerobic exercise on osteopenia and muscle atrophy in type 2 diabetes mellitus model rats.
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活化的维生素D，恶甲醇和低强度有氧运动对2型糖尿病型骨质减少和肌肉萎缩的影响。
DOI：
10.1371/journal.pone.0204857
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Shimada Y
中科院分区：
文献类型：
--
作者：
Akagawa M;Miyakoshi N;Kasukawa Y;Ono Y;Yuasa Y;Nagahata I;Sato C;Tsuchie H;Nagasawa H;Hongo M;Shimada Y
糖尿病引起继发性骨质疏松和肌肉萎缩。观察了阿法骨化醇（ALF）和运动（Exe）对2型糖尿病（T2 DM）模型大鼠骨质疏松和骨骼肌萎缩的抑制作用。将20周龄的Otsuka Long-Evans德岛肥胖大鼠随机分配至ALF（口服0.1 μg/kg/天）、Exe（以10 m/min、60 min/天、5天/周的速度进行跑步机运动）、Comb（ALF和Exe）和Cont（用溶剂处理且不运动的T2 DM对照）组（每组n = 8-10）。将久坐的Long-Evans德岛大冢大鼠用作非高吞噬对照。治疗2周或6周后，测量血糖（BG）水平、胫骨前肌纤维横截面积（CSA）、股骨骨矿物质密度（BMD）以及通过实时聚合酶链反应测定评估的比目鱼肌的肌肉合成代谢标志物（Pax 7、MyoD和肌细胞生成素）和分解代谢标志物（Atrogin-1、MuRF 1和REDD 1）的相对量。与对照组相比，Exe和Comb治疗6周可降低BG水平。ALF、Exe和Comb治疗2周和6周后，CSA恢复情况与对照组相比。与对照组相比，ALF和Comb治疗6周增加股骨BMD。治疗2周后，Comb治疗增加了MyoD表达，降低了MuRF 1表达。ALF或Exe单药治疗2周后分别显著降低Atrogin-1或MuRF 1表达。治疗6周后，ALF和Comb治疗降低了Atrogin-1和REDD 1。这些结果表明，ALF和Exe的组合通过刺激骨骼肌分化和抑制肌肉分解代谢基因从治疗的早期阶段改善CSA。观察到BG、BMD和CSA的改善是联合治疗的长期效应。观察到肌肉分解代谢基因的持续抑制作为这些效应的背景。
Diabetes mellitus causes secondary osteoporosis and muscle atrophy. The ability of alfacalcidol (ALF) and exercise (Exe) to inhibit osteoporosis and muscle atrophy in type 2 diabetes mellitus (T2DM) model rats was examined. Twenty-week-old Otsuka Long-Evans Tokushima Fatty rats were randomized to ALF (orally 0.1 μg/kg/day), Exe (treadmill exercise at 10 m/min, 60 min/day, 5 days/week), Comb (ALF and Exe), and Cont (T2DM control treated with vehicle and no exercise) groups (n = 8–10 per group). Sedentary Long-Evans Tokushima Otsuka rats were used as a non-hyperphagic control. After treatment for 2 or 6 weeks, blood glucose (BG) levels, cross-sectional area (CSA) of tibialis anterior muscle fibers, femoral bone mineral density (BMD), and relative quantities of muscle anabolic markers (Pax7, MyoD, and myogenin) and catabolic markers (Atrogin-1, MuRF1, and REDD1) of the soleus muscle assessed by real-time polymerase chain reaction assays were measured. Exe and Comb treatments for 6 weeks decreased BG levels compared with those of the Cont group. ALF, Exe, and Comb treatments for 2 and 6 weeks recovered the CSA compared with that of the Cont group. ALF and Comb treatments for 6 weeks increased femoral BMDs compared with those of the Cont group. After 2 weeks of treatment, Comb treatment increased MyoD expression and decreased MuRF1 expression. ALF or Exe monotherapy significantly decreased Atrogin-1 or MuRF1 expression after 2 weeks of treatment, respectively. After 6 weeks of treatment, ALF and Comb treatments decreased Atrogin-1 and REDD1. These results demonstrate that a combination of ALF and Exe improved CSA from the early phase of treatment by stimulating skeletal muscle differentiation and suppressing muscle catabolic genes. Improvements in BG, BMD, and CSA were observed as long-term effects of the combination therapy. Continued suppression of muscle catabolic genes was observed as a background to these effects.
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