The Effects of Exendin-4 on IRS-2 Expression and Phosphorylation in INS-1 Cells / 당뇨병
Korean Diabetes Journal
; : 102-111, 2008.
Article
em Ko
| WPRIM
| ID: wpr-61110
Biblioteca responsável:
WPRO
ABSTRACT
BACKGROUND:
Insulin receptor substrate 2 (IRS-2) is a key regulator of beta cell proliferation and apoptosis. This study was aimed to investigate effect of the glucolipotoxicity on apoptosis in INS-1 cell, and the effect of Exendin-4, a GLP-1 receptor agonist, on IRS-2 expression in the glucolipotoxicity induced INS-1 cell. The goal was to discover the new action mechanism and function of Exendin-4 in beta cell apoptosis.METHOD:
INS-1 cells were cultured in glucolipotoxic condition for 2, 4 or 6 days and were categorized as G groups. Another group in which 50 nM Exendin-4 was added to INS-1 cells, cultured in glucolipotoxic condition, were named as Ex-4 groups. We investigated the expression of IRS-2 by RT-PCR, phosphorylated IRS-2 and phosphorylated Akt protein levels by western blot. We measured the apoptosis ratio of INS-1 cell in glucolipotoxic condition by TUNEL staining in both groups.RESULT:
IRS-2 expression of INS-1 cells decreased with correlation to the time of exposure to glucolipotoxic condition. pIRS-2 and pAkt protein levels decreased in the similar pattern in glucolipotoxicity group. However, this effect of glucolipotoxicity on INS-1 cell was inhibited by the Exendin-4 treatment. In the Ex-4 groups, IRS-2 expression, pIRS-2 and pAkt protein levels remained at the similar level to low glucose condition state. Also, apoptosis induced by glucolipotoxicity was suppressed by Exendin-4 treatment significantly.CONCLUSION:
We showed that the long-term treatment of Exendin-4 inhibited the apoptosis of beta cells significantly in glucolipotoxic condition and that this effect of Exendin-4 was related with IRS-2 and Akt among the beta cell's intracellular signal transduction pathway.Palavras-chave
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Assunto principal:
Peptídeos
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Fosforilação
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Peçonhas
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Transdução de Sinais
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Células Cultivadas
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Western Blotting
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Apoptose
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Receptores de Glucagon
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Marcação In Situ das Extremidades Cortadas
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Proliferação de Células
Idioma:
Ko
Revista:
Korean Diabetes Journal
Ano de publicação:
2008
Tipo de documento:
Article