The Effects of Exendin-4 on IRS-2 Expression and Phosphorylation in INS-1 Cells.
10.4093/kdj.2008.32.2.102
- Author:
Ji Hyun KIM
1
;
Ji Won KIM
;
Sung Yoon JEON
;
Heon Seok PARK
;
Dong Sik HAM
;
Young Hye YOU
;
Seung Hwan LEE
;
Jae Hyoung CHO
;
Mi Ja KANG
;
Kang Woo LEE
;
Hyuk Sang KWON
;
Kun Ho YOON
;
Bong Yun CHA
;
Kwang Woo LEE
;
Sung Koo KANG
;
Ho Young SON
Author Information
1. Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Korea.
- Publication Type:Original Article
- Keywords:
Exenatide;
Insulin receptor substrate 2;
INS-1 cell
- MeSH:
Apoptosis;
Blotting, Western;
Cell Proliferation;
Cells, Cultured;
Glucagon-Like Peptide 1;
Glucagon-Like Peptide-1 Receptor;
Glucose;
In Situ Nick-End Labeling;
Insulin Receptor Substrate Proteins;
Peptides;
Phosphorylation;
Receptors, Glucagon;
Signal Transduction;
Venoms
- From:Korean Diabetes Journal
2008;32(2):102-111
- CountryRepublic of Korea
- Language:Korean
-
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.
