Muscle wasting is a complication in patients with diabetes and leads to a reduced quality of life. However, the detailed mechanisms of diabetes-induced muscle wasting remain unknown. Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor that suppresses plasminogen activator activity, is involved in the pathophysiology of various diseases, including diabetes. In the present study, we examined the role of endogenous PAI-1 in the decrease in muscle mass and the impaired grip strength induced by the diabetic state by employing streptozotocin (STZ)-treated PAI-1-deficient female mice. The analyses of skeletal muscles and grip strength were performed in PAI-1-deficient and wild-type mice 4 weeks after the induction of a diabetic state by STZ administration. PAI-1 deficiency did not affect muscle mass in the lower limbs measured by quantitative computed tomography or tissue weights of the tibialis anterior, gastrocnemius and soleus muscles of female mice with or without STZ treatment. On the other hand, PAI-1 deficiency significantly aggravated grip strength decreased by STZ in female mice. PAI-1 deficiency did not affect the mRNA levels of Pax7, MyoD, myogenin or myosin heavy chain in either the tibialis anterior or soleus muscles of female mice with or without STZ treatment. In conclusion, we revealed for the first time that PAI-1 deficiency aggravates grip strength impaired by the diabetic state in female mice, although it did not affect diabetes-decreased muscle mass.

肌肉萎缩是糖尿病患者的一种并发症，会导致生活质量下降。然而，糖尿病引起的肌肉萎缩的详细机制仍然未知。纤溶酶原激活物抑制剂-1 (PAI-1) 是一种抑制纤溶酶原激活物活性的丝氨酸蛋白酶抑制剂，参与多种疾病的病理生理学，包括糖尿病。在本研究中，我们通过使用链脲佐菌素 (STZ) 治疗的 PAI-1 缺陷雌性小鼠检查了内源性 PAI-1 在糖尿病状态引起的肌肉质量减少和握力受损中的作用。在通过 STZ 给药诱导糖尿病状态 4 周后，在 PAI-1 缺陷型和野生型小鼠中进行骨骼肌和握力分析。PAI-1 缺乏不影响通过定量计算机断层扫描测量的下肢肌肉质量或接受或不接受 STZ 治疗的雌性小鼠胫骨前肌、腓肠肌和比目鱼肌的组织重量。另一方面，PAI-1 缺乏显着加重了 STZ 对雌性小鼠的握力下降。PAI-1 缺乏不影响接受或不接受 STZ 治疗的雌性小鼠胫骨前肌或比目鱼肌中 Pax7、MyoD、肌细胞生成素或肌球蛋白重链的 mRNA 水平。总之，我们首次揭示 PAI-1 缺乏会加重雌性小鼠糖尿病状态导致的握力受损，尽管它不会影响糖尿病导致的肌肉质量下降。接受或不接受 STZ 治疗的雌性小鼠的腓肠肌和比目鱼肌。另一方面，PAI-1 缺乏显着加重了 STZ 对雌性小鼠的握力下降。PAI-1 缺乏不影响接受或不接受 STZ 治疗的雌性小鼠胫骨前肌或比目鱼肌中 Pax7、MyoD、肌细胞生成素或肌球蛋白重链的 mRNA 水平。总之，我们首次揭示 PAI-1 缺乏会加重雌性小鼠糖尿病状态导致的握力受损，尽管它不会影响糖尿病导致的肌肉质量下降。接受或不接受 STZ 治疗的雌性小鼠的腓肠肌和比目鱼肌。另一方面，PAI-1 缺乏显着加重了 STZ 对雌性小鼠的握力下降。PAI-1 缺乏不影响接受或不接受 STZ 治疗的雌性小鼠胫骨前肌或比目鱼肌中 Pax7、MyoD、肌细胞生成素或肌球蛋白重链的 mRNA 水平。总之，我们首次揭示 PAI-1 缺乏会加重雌性小鼠糖尿病状态导致的握力受损，尽管它不会影响糖尿病导致的肌肉质量下降。经或未经 STZ 处理的雌性小鼠胫骨前肌或比目鱼肌中的肌细胞生成素或肌球蛋白重链。总之，我们首次揭示 PAI-1 缺乏会加重雌性小鼠糖尿病状态导致的握力受损，尽管它不会影响糖尿病导致的肌肉质量下降。经或未经 STZ 处理的雌性小鼠胫骨前肌或比目鱼肌中的肌细胞生成素或肌球蛋白重链。总之，我们首次揭示 PAI-1 缺乏会加重雌性小鼠糖尿病状态导致的握力受损，尽管它不会影响糖尿病导致的肌肉质量下降。