title: IGF-1 induces hypoxia-inducible factor 1α-mediated GLUT3 expression through PI3K/Akt/mTOR dependent pathways in PC12 cells.
abstract: Glucose metabolism is essential for most mammalian neurons, and the passage of glucose across cell membranes is mainly facilitated by glucose transporter 3 (GLUT3). In ischemia/reperfusion injured brains, increase of IGF-1 secretion and GLUT3 up-regulation, are regarded as protective processes. Recent works have shown that various growth factors and cytokines including IGF-1 can stimulate HIF-1α expression, thereby triggering transcription of numerous hypoxia-inducible genes by oxygen-independent mechanisms. So, we hypothesized that HIF-1α might play important role in the process of IGF-1 induced GLUT3. Using echinomycin, a HIF-1 inhibitor, and HIF-1α siRNA, we demonstrated IGF-1 induced GLUT3 expression through HIF-1α in neuronal PC12 cells. Moreover, IGF-1 stimulated HIF-1α and GLUT3 protein expression through phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR dependent pathways. Analysis of GLUT3 promoter deletion sequences indicated that a putative hypoxia-response element (HRE) was critical in GLUT3 promoter activity when PC12 cells were treatment with CoCl(2) and IGF-1. In conclusion, we showed that the expression of GLUT3 in response to IGF-1 was dependent on PI-3-kinase and mTOR activity, and required the transcription factor HIF-1α.
authors: Department of Neurosurgery, The Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China.
authors: Jian
authors: J
authors: Yu
authors: Junliang
authors: J
authors: Li
authors: Shanyi
authors: S
authors: Zhang
authors: Xinke
authors: X
authors: Xu
authors: Meiguang
authors: M
authors: Zheng
authors: Guangyi
authors: G
authors: Jiang
authors: Fangcheng
authors: F
authors: Li
mesh_terms: D000818:Animals; D051274:Glucose Transporter Type 3 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: D051274:Glucose Transporter Type 3; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C497444:Hif1a protein, rat; C546845:mTOR protein, rat