The Myostatin On Myoblast Glucose Metabolism

Myostatin (MSTN) is a growth factor, which is secreted by skeletal muscle and inhibits the growth and proliferation of skeletal muscle itself. It has a crucial role on the regulation of skeletal muscle homeostasis. Since MSTN can be distributed to the whole body by circulation, its function may not only be limited in skeletal muscle. It has been identified that the adipo-tissue could be regulated by MSTN. The increased expression of Myostatin gene during some diseases progression will cause the degradation of structure proteins in skeletal muscle, and followed by cachexia. Thus, MSTN shouldn't be only consided as a regulator of skeletal muscle mass, but also an endocrine factor, which may participate the regulation of metabolism of lipid and proteins etc.Our project mainly focused on the affect of MSTN on glucose metabolism in celll culture system. The results of glucose consumption assay show that MSTN could promote the glucose consumption in differentiated C2C2 myotubes. Those promotion effects were similar to Insulin, and the combination of those two drugs could synergize with each other. The function of MSTN on glucose consumption didn't depend on other hormones or factors in the serum, nor relate to the cyto-toxicity of MSTN. Since MSTN couldn't promote the glucose metabolism in undifferentiated myoblasts, its function may rely on the GLUT4, which only appears in differentiated myotubes. The RT-PCR results suggested that MSTN couldn't upregulate the GLUT4 transcription, which indicate that MSTN may have effect on the translocation of GLUT4 from cytosol to cell membrane.Interestingly, in the GLUT4 deficient chicken myotubes, the promotion effects of Insulin on glucose consumption were not that apparent like in mice, while MSTN's effects were still obviously. Those results indicated that other types of glucose transporter might involve in MSTN's promotion effects on glucose metabolism. However, the glucose uptake experiments were contradictorily. MSTN could inhibit the glucose uptake in short time. But if we pretreat the cells with MSTN for 1h, wash with PBS, and then test the glucose uptake, MSTN could promote the uptake again. The explanation of those outwardly contrary results is: The two kinds of experiments adopted different strategy and object. The glucose uptake experiments are instantaneous, while the glucose consumption assays last for long term, which is a combination effect of several types of glucose transporter.Our researches try to elucidate the regulation mechanism of MSTN on skeletal muscle glucose metabolism. Its results will provide a new clue on relationship between skeletal muscle and type 2 diabetes or insulin resistance, and also a novel target of diabetes therapy.