Vignaud A, Ramond F, Hourdé C, Keller A, Butler-Browne G, Ferry A
INSERM U787 and Université Pierre et Marie Curie-Paris 6, Paris, France.
Pathobiology. 2007;74(5):291-300. doi: 10.1159/000105812.
It is of common knowledge that diabetes decreases skeletal muscle contractility and induces atrophy. However, how hyperglycemia and insulin deficiency modify muscle mass and neuromuscular recovery after muscle injury is not well known. We have analyzed two models of diabetes: streptozotocin (STZ)-treated Swiss mice and Akita mice that spontaneously develop diabetes. A fast muscle, the tibialis anterior, was injured following injection of a myotoxic agent (cardiotoxin). Neuromuscular function was evaluated by examining in situ isometric contractile properties of regenerating muscles in response to nerve stimulation 14, 28 and 56 days after myotoxic injury. We found that STZ-induced diabetes reduces muscle weight and absolute maximal tetanic force in both regenerating and uninjured muscles (p = 0.0001). Moreover, it increases specific maximal tetanic force and tetanic fusion in regenerating and uninjured muscles (p = 0.04). In the Akita mice, diabetes decreases muscle weight and absolute maximal tetanic force, and increases tetanic fusion in both regenerating and uninjured muscles (p < or = 0.003). Interestingly, STZ-induced diabetes exerts more marked effects than diabetes of genetic origin, in particular on muscle weight. This reduction in muscle mass was not due to an increased expression of the atrogenes MuRF1 and atrogin-1 during STZ-induced diabetes. The present study in mice demonstrates that both models of diabetes impair regenerating muscles as well as uninjured muscles. Regenerating fast muscles are weaker, lighter and slower in diabetic compared with nondiabetic mice.
众所周知，糖尿病会降低骨骼肌收缩力并导致萎缩。然而，高血糖和胰岛素缺乏如何改变肌肉损伤后的肌肉质量和神经肌肉恢复情况尚不清楚。我们分析了两种糖尿病模型：链脲佐菌素（STZ）处理的瑞士小鼠和自发患糖尿病的秋田小鼠。一块快肌，即胫前肌，在注射肌毒性剂（心脏毒素）后受到损伤。在肌毒性损伤后14、28和56天，通过检测再生肌肉对神经刺激的原位等长收缩特性来评估神经肌肉功能。我们发现，STZ诱导的糖尿病会降低再生肌肉和未损伤肌肉的肌肉重量和绝对最大强直力（p = 0.0001）。此外，它会增加再生肌肉和未损伤肌肉的比最大强直力和强直融合（p = 0.04）。在秋田小鼠中，糖尿病会降低肌肉重量和绝对最大强直力，并增加再生肌肉和未损伤肌肉的强直融合（p≤0.003）。有趣的是，STZ诱导的糖尿病比遗传性糖尿病产生的影响更显著，尤其是对肌肉重量的影响。在STZ诱导的糖尿病期间，肌肉质量的这种减少并非由于萎缩相关基因MuRF1和atrogin - 1的表达增加所致。本研究在小鼠中表明，两种糖尿病模型都会损害再生肌肉和未损伤肌肉。与非糖尿病小鼠相比，糖尿病小鼠的再生快肌更弱、更轻且恢复更慢。
