1946-P: Insulin-Like Growth Factor-1 Protects against the Detrimental Effects of Advanced Glycation End Products and High Glucose in Myoblastic C2C12 Cells

Abstract

Previous studies have shown that diabetes mellitus increases the risk of sarcopenia. We previously reported that higher serum advanced glycation end product (AGE) and lower serum insulin-like growth factor-I (IGF-I) were independently associated with muscle mass reduction in patients with type 2 diabetes. The present study examined effects of AGEs and IGF-I on myogenic differentiation and apoptosis in C2C12 cells. Real-time PCR and western blot analyses showed that AGE3 significantly decreased the mRNA and protein expressions of MyoD and Myogenin, whereas IGF-I significantly increased them and reversed the effects of AGE3. AGE3 significantly decreased endogenous IGF-I expression and suppressed IGF-I-induced Akt activation. High glucose (22 mM), but not AGE3, significantly increased expression of receptor for AGEs (RAGE), while IGF-I significantly decreased it. Moreover, 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. To investigate whether high glucose enhances the AGE3’ effects, the effects of co-treatment with high glucose and AGE3 were examined. Although high glucose alone did not affect the apoptosis of C2C12 cells, it enhanced AGE3-induced apoptosis. IGF-I significantly reversed the effects of co-incubation of high glucose and AGEs on the expression of MyoD and Myogenin as well as the apoptosis. These findings indicate that AGE3 inhibits myogenic differentiation and increases 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 reversed 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. Disclosure I. Kanazawa: None. N. Adachi: None. K. Tanaka: None. A. Takeno: None. M. Notsu: None. S. Tanaka: None. T. Sugimoto: None.