Ghrelin Modulates Insulin Sensitivity and Tau Phosphorylation in High Glucose-Induced Hippocampal Neurons

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概要

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• 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 Alzheimers 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 [3H]-2-deoxy-D-glucose uptake. The expression of Akt, glycogen synthase kinase-3β (GSK-3β) 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-3β phosphorylation, whereas phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin eliminated ghrelins 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.

著者

• WANG Wei

  Department of Mechanical Engineering, Chiba University

• Chen Ying

  Department of Endocrinology, First Hospital of China Medical University

• Cao Cui-Ping

  Department of Endocrinology, First Hospital of China Medical University

• Li Chun-Ri

  College of Acupuncture and Moxibustion, Liaoning Traditional Chinese Medical University

• Zhang Dan

  Department of Endocrinology, First Hospital of China Medical University

• Han Ling-Ling

  Department of Endocrinology, First Hospital of China Medical University

• Zhang Xiao-Qing

  College of Acupuncture and Moxibustion, Liaoning Traditional Chinese Medical University

• Kim Andre

  Department of Pharmaceutical Engineering, College of Medical Life Science, Silla University

• Kim Suhkmann

  Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University

• Liu Guo-Liang

  Department of Endocrinology, First Hospital of China Medical University

• Zhang Dan

  Department Of Computer Science And Communication Engineering

• Chen Ying

  Department Of Anatomy The First Medical University Of Pla

• Wang Wei

  Department Of Biology Graduate School Chinese Academy Of Sciences Beijing

• Wang Wei

  Department Of Biochemistry Hainan Medical College

• Wang Wei

  Department of Endocrinology, the Second Affiliated Hospital, Harbin Medical University

• CHEN Ying

  Department of Anatomy , The First Medical University of PLA

• Wang Wei

  Department of Anesthesiology, China-Japan Friendship Hospital, the Chinese Ministry of Health, Beijing, China

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