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KMID : 1199120080320020102
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Korean Diabetes Journal
2008 Volume.32 No. 2 p.102 ~ p.111
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The Effects of Exendin-4 on IRS-2 Expression and Phosphorylation in INS-1 Cells
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Kim Ji-Hyun
Kim Ji-Won
Jeon Sung-Yoon
Park Heon-Seok
Ham Dong-Sik
You Young-Hye
Lee Seung-Hwan
Cho Jae-Hyoung
Kang Mi-Ja
Lee Kang-Woo
Kwon Hyeok-Sang
Yoon Kun-Ho
Cha Bong-Yun
Lee Kwang-Woo
Kang Sung-Koo
Son Ho-Young
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Abstract
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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. (KOREAN DIABETES J 32:102-111, 2008)
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KEYWORD
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Exenatide, Insulinreceptorsubstrate2, NS-1cell
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