Dysfunction of muscle contraction with impaired intracellular Ca2+ handling in skeletal muscle and the effect of exercise training in male db/db mice
Dysfunction of muscle contraction with impaired intracellular Ca2+ handling in skeletal muscle and the effect of exercise training in male db/db mice
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DOI：
10.1152/japplphysiol.00048.2018
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Watada, Hirotaka
中科院分区：
文献类型：
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作者：
Eshima, Hiroaki;Tamura, Yoshifumi;Watada, Hirotaka
2型糖尿病的特征在于骨骼肌收缩力产生减少和疲劳性增加。虽然在肌肉收缩期间维持Ca 2+稳态是最佳收缩功能的必要条件，但2型糖尿病中肌肉收缩功能障碍的潜在机制尚不清楚。在这里，我们研究了骨骼肌收缩力和Ca 2+流量在收缩和药物刺激2型糖尿病模型小鼠（db/db小鼠）。此外，我们还研究了跑台运动训练对肌肉收缩功能的影响。在雄性db/db小鼠中，与对照小鼠相比，在强直刺激快缩肌期间，肌肉收缩力和峰值Ca 2+水平均较低，而刺激后Ca 2+积累较高。虽然6周的运动训练并没有改善葡萄糖耐量，运动确实改善了肌肉收缩功能障碍，峰值Ca 2+水平，和Ca 2+积累刺激后，在雄性db/db小鼠。这些数据表明，功能失调的Ca 2+流量可能会导致骨骼肌收缩功能障碍，在2型糖尿病和运动训练可能是一个有前途的治疗方法，为功能失调的骨骼肌contraction.NEW & NOTEWORTHY本研究的目的是检查肌肉收缩功能和Ca 2+调节以及运动训练的影响，在骨骼肌肥胖糖尿病小鼠（db/db）。我们观察到男性2型糖尿病动物模型的肌肉收缩力和Ca 2+调节受损。运动训练6周后，这些肌肉功能障碍均得到改善。
Type 2 diabetes is characterized by reduced contractile force production and increased fatigability of skeletal muscle. While the maintenance of Ca2+ homeostasis during muscle contraction is a requisite for optimal contractile function, the mechanisms underlying muscle contractile dysfunction in type 2 diabetes are unclear. Here, we investigated skeletal muscle contractile force and Ca2+ flux during contraction and pharmacological stimulation in type 2 diabetic model mice (db/db mice). Furthermore, we investigated the effect of treadmill exercise training on muscle contractile function. In male db/db mice, muscle contractile force and peak Ca2+ levels were both lower during tetanic stimulation of the fast-twitch muscles, while Ca2+ accumulation was higher after stimulation compared with control mice. While 6 wk of exercise training did not improve glucose tolerance, exercise did improve muscle contractile dysfunction, peak Ca2+ levels, and Ca2+ accumulation following stimulation in male db/db mice. These data suggest that dysfunctional Ca2+ flux may contribute to skeletal muscle contractile dysfunction in type 2 diabetes and that exercise training may be a promising therapeutic approach for dysfunctional skeletal muscle contraction.NEW & NOTEWORTHY The purpose of this study was to examine muscle contractile function and Ca2+ regulation as well as the effect of exercise training in skeletal muscle in obese diabetic mice (db/db). We observed impairment of muscle contractile force and Ca2+ regulation in a male type 2 diabetic animal model. These dysfunctions in muscle were improved by 6 wk of exercise training.