Role Of GDF11 In Skeletal Muscle Insulin Resistance

Objective: GDF11 recently has been reported to rejuvenate skeletal muscle,heart and brain in aged mice.And the aged skeletal muscle is closely related to insulin resistance.We wondered whether GDF11 have an effect on skeletal muscle insulin resistance.Methods: High fat diet(HFD)induced obese mice with insulin resistance were established in vivo.IPGTT and ITT in each group were tested.The serum levels of GDF11 and the expression of GDF11 in skeletal muscle were measured.Then,in vitro,GDF11 was given to C2C12 induced by palmitate.The glucose uptake was measured by 2NBDG uptake assay and the expression of GDF11,GLUT4,IRS-1 and PGC-1α in C2C12 were tested.Results:(1)In vivo: compared with the low fat diet(LFD)group,the weight of the mice in HFD group was significantly increased,the glucose tolerance was impaired and insulin sensitivity was decreased(P<0.05);Compared with the LFD group,the levels of GDF11 in serum and in skeletal muscle of HFD group were significantly lower(P<0.05).(2)In vitro: compared with the control group,the expression of GDF11 in C2C12 myotubes was significantly decreased after palmitate treatment(P<0.05).The glucose uptake and the expression of GLUT4 and IRS-1 were significantly decreased after treatment by palmitate(P<0.05).After treatment by GDF11,there was no significant change in glucose uptake and the expression of GLUT4 and IRS-1 in myotubes(P>0.05).(3)Compared with the control group,the expression of PGC-1α in myotubes was significantly decreased after the intervention of palmitate(P<0.05),There was no significant difference in the expression of PGC-1α after GDF11 treatment(P>0.05).Conclusions: We firstly confirmed that the expression of GDF11 decreased both in the skeletal muscle of obese mice and palmitate treated myotubes,but supplementation with GDF11 did not ameliorate the palmitate induced insulin resistance in C2C12 myotubes.