TY - JOUR
T1 - Insulin-Like Growth Factor-I Protects Against the Detrimental Effects of Advanced Glycation End Products and High Glucose in Myoblastic C2C12 Cells
AU - Adachi, Naoko
AU - Kanazawa, Ippei
AU - Tanaka, Ken ichiro
AU - Takeno, Ayumu
AU - Notsu, Masakazu
AU - Tanaka, Sayuri
AU - Sugimoto, Toshitsugu
N1 - Funding Information:
Funding This work was supported in part by a Grant-in-Aid for Scientific Research (C) (Grant No. 16K09240) and a research grant from Eli Lilly Japan.
Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/7/15
Y1 - 2019/7/15
N2 - 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 24 h 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 (22 mM) 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.
AB - 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 24 h 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 (22 mM) 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.
UR - http://www.scopus.com/inward/record.url?scp=85062479604&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062479604&partnerID=8YFLogxK
U2 - 10.1007/s00223-019-00537-w
DO - 10.1007/s00223-019-00537-w
M3 - Article
C2 - 30809689
AN - SCOPUS:85062479604
SN - 0171-967X
VL - 105
SP - 89
EP - 96
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 1
ER -