Insulin-Like Growth Factor-I Protects Against the Detrimental Effects of Advanced Glycation End Products and High Glucose in Myoblastic C2C12 Cells
Insulin-Like Growth Factor-I Protects Against the Detrimental Effects of Advanced Glycation End Products and High Glucose in Myoblastic C2C12 Cells
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DOI：
10.1007/s00223-019-00537-w
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发表时间：
2019-07-01
影响因子：
4.2
通讯作者：
Sugimoto, Toshitsugu
中科院分区：
文献类型：
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作者：
Adachi, Naoko;Kanazawa, Ippei;Sugimoto, Toshitsugu
既往研究表明，糖基化终末产物（AGEs）和胰岛素样生长因子-I（IGF-I）参与了糖尿病性肌减少症的发病机制。在这项研究中，我们研究了AGEs和/或IGF-I处理24小时对小鼠成肌细胞C2 C12成肌分化和凋亡的影响。采用Real-time PCR和Western blot检测细胞mRNA和蛋白表达，DNA片段检测ELISA试剂盒检测细胞凋亡。AGE 3显著降低MyoD和Myogenin的mRNA和蛋白表达，而IGF-I显著增加它们并减弱AGE 3的作用。AGEs显著降低内源性IGF-I mRNA表达，抑制IGF-I诱导的Akt激活。高糖（22 mM）显著增加AGEs受体Rage mRNA表达，IGF-I显著降低AGEs受体Rage mRNA表达，DNA片段ELISA显示AGE 2和AGE 3显著增加C2 C12细胞凋亡，IGF-I显著抑制AGE 2和AGE 3诱导的C2 C12细胞凋亡。与此相反，高糖增强AGE 3诱导的细胞凋亡。IGF-I可显著减弱高糖+AGE 3对MyoD和Myogenin mRNA和蛋白表达及细胞凋亡的影响。这些结果表明，AGEs抑制C2 C12细胞的肌源性分化和增加凋亡，而高糖则增加AGEs诱导的C2 C12细胞的凋亡，这表明AGEs和高糖可能有助于减少肌肉质量和功能。此外，IGF-I减弱了AGEs和高糖对成肌细胞的不利影响，因此，IGF-I-Akt信号可能是DM诱导的肌肉减少症的治疗靶点。
Previous studies suggested that advanced glycation end products (AGEs) and insulin-like growth factor-I (IGF-I) are involved in the mechanism of diabetes-induced sarcopenia. In this study, we examined effects of treatments with AGEs and/or IGF-I for 24h on myogenic differentiation and apoptosis in mouse myoblastic C2C12 cells. Real-time PCR and Western blot were performed to investigate mRNA and protein expressions, and apoptosis was examined by using a DNA fragment detection ELISA kit. AGE3 significantly decreased mRNA and protein expressions of MyoD and Myogenin, whereas IGF-I significantly increased them and attenuated the effects of AGE3. AGEs significantly decreased endogenous IGF-I mRNA expression and suppressed IGF-I-induced Akt activation. High glucose (22mM) significantly increased mRNA expression of Rage, a receptor for AGEs, while IGF-I significantly decreased it. DNA fragment ELISA showed that AGE2 and AGE3 significantly increased apoptosis of C2C12 cells, whereas IGF-I significantly suppressed the AGE2- and AGE3-induced apoptosis. In contrast, high glucose enhanced AGE3-induced apoptosis. IGF-I significantly attenuated the effects of high glucose plus AGE3 on the mRNA and protein expressions of MyoD and Myogenin as well as the apoptosis. These findings indicate that AGEs inhibit myogenic differentiation and increase apoptosis in C2C12 cells, and that high glucose increases RAGE and enhances the AGE3-induced apoptosis, suggesting that AGEs and high glucose might contribute to the reduction of muscle mass and function. Moreover, IGF-I attenuated the detrimental effects of AGEs and high glucose in myoblastic cells; thus, IGF-I-Akt signal could be a therapeutic target of DM-induced sarcopenia.