title: Insulin increases glutamate transporter GLT1 in cultured astrocytes.
abstract: The astroglial cell-specific glutamate transporter subtype 2 (excitatory amino acid transporter 2, GLT1) plays an important role in excitotoxicity that develops after damage to the central nervous system (CNS) is incurred. Both the protein kinase C signaling pathway and the epidermal growth factor (EGF) pathway have been suggested to participate in the modulation of GLT1, but the modulatory mechanisms of GLT1 expression are not fully understood. In the present study, we aimed to evaluate the effects of insulin on GLT1 expression. We found that short-term stimulation of insulin led to the upregulation of both total and surface expressions of GLT1. Akt phosphorylation increased after insulin treatment, and triciribine, the inhibitor of Akt phosphorylation, significantly inhibited the effects of insulin. We also found that the upregulation of GLT1 expression correlated with increased kappa B motif-binding phosphoprotein (KBBP) and GLT1 mRNA levels. Our results suggest that insulin may modulate the expression of astrocytic GLT1, which might play a role in reactive astrocytes after CNS injuries.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, PR China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Ji
authors.forename: Si-Min
authors.initials: SM
authors.lastname: Xu
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis* / Q000235:genetics; D007328:Insulin / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D007328:Insulin; D012333:RNA, Messenger; C493395:Slc1a2 protein, rat; D051057:Proto-Oncogene Proteins c-akt