Mammalian target of rapamycin (mTOR) is involved in the neuronal differentiation of neural progenitors induced by insulin.
The fate of neural progenitor cells (NPCs) is determined by many extracellular cues. Among them, insulin and insulin-like growth factor (IGF) family are found to promote the neuronal differentiation of NPCs. Akt activation has been indicated to be responsible for the insulin/IGF-I induced neuronal differentiation. However, the mechanism by which insulin/IGF-I-PI3K-Akt pathway induces neurogenesis of NPCs is not clear. In this study, we have demonstrated that mTOR is involved in the insulin-induced neuronal differentiation. Insulin induces neurogenesis of NPCs in a dose-dependent manner. Phosphorylated mTOR has been up-regulated in a PI3K-Akt dependent manner during NPC differentiation induced by insulin. The specific inhibitor of mTOR, rapamycin, can abrogate the increase of differentiated neurons stimulated by insulin. In addition, this is not the result from the apoptosis of neurons or NPCs. This research has extended the understanding of functions of mTOR and the mechanism of NPC differentiation regulated by insulin.
Han
Jin
J
Key laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China.
Wang
Bin
B
Xiao
Zhifeng
Z
Gao
Yuan
Y
Zhao
Yanhong
Y
Zhang
Jing
J
Chen
Bing
B
Wang
Xia
X
Dai
Jianwu
J
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D020123:Sirolimus / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D007166:Immunosuppressive Agents; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human