Expression Of CaMK And HDAC5 Relations In Rat Skeletal Muscle GLUT4 Hyperglycemic Caffeine-induced Insulin Resistance

Objective: To use the methods of feeding with highcarbohydrates72h to establish the insulin resistance model, and to use the methods offeeding with low carbohydrates48h and fasting24h to set up the insulin sensitivitymodel. To observe the changes of GLUT4expression in the high or low carbohydratesconcentrations and the phosphorylation CaMKⅡ(Thr286)、HDAC5(Ser498) andHDAC5(Ser259）in the skeletal muscle cells. And to observe the role of CaMKⅡ(Thr286) which was induced by KN62in lower the HDAC5(Ser498) andHDAC5(Ser259）phosphorylation and GLUT4expression, and to find out whether theeffects of Caffeine on regulating the GLUT4expression were related with Caffeine—Ca2+—CaMKⅡ—HDAC5signal pathway. Method:42male Wistar rats whichwere8-week-old were randomly divided into four groups (n=12), named as HGCgroup, HGK group, LGC group and LGK group. The rats were fed with different dietand induced by Caffeine or KN62. And CaMKⅡ(Thr286)、HDAC5(Ser498) andHDAC5(Ser259）phosphorylation and GLUT4protein expression were tested bywestern blotting. Results: Compared with the LGK group, both CaMKⅡ(Thr286)and HDAC5(Ser259）andHDAC5(Ser498）phosphorylation increased significantly inskeletal muscle cells in LGC group. Compared with the LGK and LGC group, CaMKⅡ(Thr286)、HDAC5(Ser498) and HDAC5(Ser259）phosphorylation decreasedobviously in HGC and HGK group. Meanwhile, the changes of CaMKⅡ(Thr286)、HDAC5(Ser498) and HDAC5(Ser259） phosphorylation in HGC group had nosignificant difference with that in HGK group. Conclusion:(1) Caffeine couldremarkably increase the expression of GLUT4, and increase the CaMKⅡ(Thr286)、HDAC5(Ser498) and HDAC5(Ser259） phosphorylation and exist a remarkablypositive correlation. While KN62could significantly decrease the CaMKⅡ(Thr286)、HDAC5(Ser498) and HDAC5(Ser259）phosphorylation and the expression GLUT4.They demonstrated that the effects of Ca2+signal which was induced by Caffeine onincreasing the expression of GLUT4were possibly related with Caffeine—Ca2+—CaMK Ⅱ—HDAC5signal pathway.(2) Whatever the rats were fed with, theexpression of GLUT4was corresponded with CaMKⅡ(Thr286)、HDAC5(Ser498)and HDAC5(Ser259) in skeletal muscle cells. So the effects of CaMKⅡon regulatingthe expression of GLUT4in skeletal muscle were related with inducing HDAC5andregulating its (Ser498) site and（Ser259）site.