Protective Effects of Glucagon Like Peptide-1 on HIT-T15 beta Cell Apoptosis via ER Stress Induced by 2-deoxy-D-glucose.
10.4093/kdj.2008.32.6.477
- Author:
Ju Young KIM
1
;
Seong Kyu LEE
;
Haing Woon BAIK
;
Ki Ho LEE
;
Hyun Jin KIM
;
Kang Seo PARK
;
Byung Joon KIM
Author Information
1. Department of Biochemistry and Molecular Biology Eulji University School of Medicine, Korea.
- Publication Type:Original Article
- Keywords:
Apoptosis;
beta cells;
ER stress;
Exendin-4;
GLP-1;
Protective effect
- MeSH:
Apoptosis;
Benzimidazoles;
Blotting, Western;
Cell Survival;
Deoxyglucose;
Endoplasmic Reticulum;
Flow Cytometry;
Glucagon;
Glucagon-Like Peptide 1;
Glucagon-Like Peptide-1 Receptor;
HSP70 Heat-Shock Proteins;
Insulin;
Insulin-Secreting Cells;
Membrane Proteins;
Peptides;
Protein Processing, Post-Translational;
Proteins;
Real-Time Polymerase Chain Reaction;
Receptors, Glucagon;
RNA, Messenger;
Venoms
- From:Korean Diabetes Journal
2008;32(6):477-487
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: The characteristic feature of pancreatic beta cells is highly developed endoplasmic reticulum (ER) due to a heavy engagement in insulin secretion. The ER serves several important function, including post-translational modification, folding, and assembly of newly synthesized secretory proteins, and its proper function is essential to cell survival. Various stress conditions can interfere with ER function. Pancreatic beta cells may be particularly vulnerable to ER stress that causes to impair insulin biosynthesis and beta cell survival through apoptosis. Glucagon like peptide-1 (GLP-1) is a new drug for treatment of type 2 diabetes and has effects on stimulation of insulin secretion and beta cell preservation. Also, it may have an antiapoptotic effect on beta cells, but detailed mechanisms are not proven. Therefore, we investigated the protective mechanism of GLP-1 in beta cells through ER stress response induced by 2-deoxy-D-glucose (2DG). METHODS: For induction of the ER stress, HIT-T15 cells (hamster beta cell line) were treated with 2DG (10 mM). Apoptosis was evaluated with MTT assay, hoechst 33342 staining and Annexin/PI flow cytometry. Expression of ER stress-related molecules was determined by real-time PCR or western blot. For blocking ER stress, we pretreated HIT-T15 cells with exendin-4 (Ex-4; GLP-1 receptor agonist) for 1 hour before stress induction. RESULTS: After induction with ER stress (2DG), beta cells were lost by apoptosis. We found that Ex-4 had a protective effect through ER stress related molecules (GRP78, GRP94, XBP-1, eIF2alpha, CHOP) modulation. Also, Ex-4 recovered the expression of insulin2 mRNA in beta cells. CONCLUSION: These results suggest that GLP-1 may protect beta cells apoptosis through ER stress modulation.
