Ghrelin modulates insulin sensitivity and tau phosphorylation in high glucose-induced hippocampal neurons.
Ghrelin, a 28-amino acid brain-gut peptide expressed in periphery tissues and the central nervous system, has been demonstrated to increase insulin sensitivity in adipocytes. Recent data have indicated that insulin resistance exists in the brain and is related to Alzheimer's Disease (AD). The aim of this study was to investigate whether ghrelin increased high glucose-induced hippocampal neuron insulin sensitivity, and further modulated tau phosphorylation. Hippocampal neurons were cultured in concentrations of 25 mM and 75 mM glucose. The effect of ghrelin on hippocampal neuronal insulin sensitivity was detected by [(3)H]-2-deoxy-D-glucose uptake. The expression of Akt, glycogen synthase kinase-3beta (GSK-3beta) and tau phosphorylation was determined via Western blotting. Culturation in 75 mM glucose resulted in decreased neuronal glucose uptake and an increase in the level of tau phosphorylation at Ser 199. In neurons treated with ghrelin for 1 h, neuronal glucose uptake was increased and tau hyperphosphorylation was improved. Ghrelin activated Akt and GSK-3beta phosphorylation, whereas phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin eliminated ghrelin's effect on neuronal glucose uptake and tau phosphorylation. This study demonstrated that ghrelin increased insulin-stimulated neuronal glucose uptake in 25 mM or 75 mM glucose, raised insulin sensitivity, improved insulin resistance and decreased tau abnormal phosphorylation via the PI3-K/Akt-GSK pathway. Ghrelin is a potential new medicine in the treatment of AD.
Chen
Ying
Y
Department of Endocrinology, First Hospital of China Medical University, Shen Yang, China.
Cao
Cui-Ping
CP
Li
Chun-Ri
CR
Wang
Wei
W
Zhang
Dan
D
Han
Ling-Ling
LL
Zhang
Xiao-Qing
XQ
Kim
Andre
A
Kim
Suhkmann
S
Liu
Guo-Liang
GL
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054439:Ghrelin / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D054439:Ghrelin; D007328:Insulin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016875:tau Proteins; D005947:Glucose