The size of skeletal muscle mass plays a significant role in glucose uptake in healthy and diabetic human subjects. Previously, we have generated myostatin-deficient (MSTN-/-) transgenic pigs via animal cloning technology. MSTN-/- pigs had dramatic phenotype with individual muscle mass increase by 100% over their wild-type controls, which provides a unique large animal model to investigate how enhanced skeletal muscles are beneficial to glucose update in diabetes. We employed intravenous administration of stretozotocin (STZ) to male MSTN-/- and wild-type pigs (100 mg/kg body weight). One month later, blood glucose and insulin concentrations and pancreas histology were examined, STZ-induced diabetes occurred in both MSTN transgenic and wild-type pigs. Histology of pancreas, analysis of pAKT and Glut4 transporter proteins by Western blotting, and real-time qPCR for MSTN gene expression were used in the study. The STZ-treated pigs had increased levels of fasting plasma glucose and insulin levels in comparison with animals receiving sodium citrate buffer, their pancreas also had reduced beta cells and slight increases in lymphocyte. There are significant lower concentrations of fasting plasma glucose and insulin in MSTN-/- pigs than that of wild-type pigs after STZ administration. Detections of pAKT and Glut4 transporter proteins by Western blotting in muscle tissue indicates significant elevations of both proteins in MSTN-/- pigs compared with the wild-type pigs. The results from this pig model suggest that enhanced skeletal muscle by manipulation of myostatin function can improve glucose uptake even in the status of diabetes.

中文翻译：

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缺乏肌肉生长抑制素的转基因猪骨骼肌生长的增强，在由链脲佐菌素诱发的糖尿病中改善了葡萄糖的摄取。

骨骼肌质量的大小在健康人和糖尿病人的葡萄糖摄取中起着重要作用。以前，我们通过动物克隆技术生成了肌生成抑制素缺乏症（MSTN-/-）转基因猪。MSTN-/-猪具有显着的表型，其单个肌肉质量比野生型对照增加了100％，这提供了一个独特的大型动物模型来研究增强的骨骼肌对糖尿病中葡萄糖更新的益处。我们对雄性MSTN-/-和野生型猪（100 mg / kg体重）采用了链脲佐菌素（STZ）静脉内给药。一个月后，检查了血糖，胰岛素浓度和胰腺组织学，在MSTN转基因和野生型猪中均出现了STZ诱导的糖尿病。胰腺组织学，通过蛋白质印迹分析pAKT和Glut4转运蛋白 本研究使用了实时定量PCR技术检测MSTN基因的表达。与接受柠檬酸钠缓冲液的动物相比，经STZ处理的猪的空腹血糖和胰岛素水平增加，其胰腺的β细胞减少，淋巴细胞略有增加。施用STZ后，MSTN-/-猪的空腹血糖和胰岛素浓度明显低于野生型猪。通过Western印迹在肌肉组织中检测到的pAKT和Glut4转运蛋白表明，与野生型猪相比，MSTN-/-猪中两种蛋白均显着升高。该猪模型的结果表明，通过控制肌肉生长抑制素功能增强骨骼肌甚至可以改善糖尿病患者的葡萄糖摄取。与接受柠檬酸钠缓冲液的动物相比，经STZ处理的猪的空腹血糖和胰岛素水平增加，其胰腺的β细胞减少，淋巴细胞略有增加。施用STZ后，MSTN-/-猪的空腹血糖和胰岛素浓度明显低于野生型猪。通过Western印迹在肌肉组织中检测到的pAKT和Glut4转运蛋白表明，与野生型猪相比，MSTN-/-猪中两种蛋白均显着升高。该猪模型的结果表明，通过控制肌肉生长抑制素功能增强骨骼肌甚至可以改善糖尿病患者的葡萄糖摄取。与接受柠檬酸钠缓冲液的动物相比，经STZ处理的猪的空腹血糖和胰岛素水平增加，其胰腺的β细胞减少，淋巴细胞略有增加。施用STZ后，MSTN-/-猪的空腹血糖和胰岛素浓度明显低于野生型猪。通过Western印迹在肌肉组织中检测到的pAKT和Glut4转运蛋白表明，与野生型猪相比，MSTN-/-猪中两种蛋白均显着升高。该猪模型的结果表明，通过控制肌肉生长抑制素功能增强骨骼肌甚至可以改善糖尿病患者的葡萄糖摄取。