Exendin-4 Protects Oxidative Stress-Induced beta-Cell Apoptosis through Reduced JNK and GSK3beta Activity.
10.3346/jkms.2010.25.11.1626
- Author:
Ju Young KIM
1
;
Dong Mee LIM
;
Chan Il MOON
;
Kyung Jin JO
;
Seong Kyu LEE
;
Haing Woon BAIK
;
Ki Ho LEE
;
Kang Woo LEE
;
Keun Young PARK
;
Byung Joon KIM
Author Information
1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Konyang University School of Medicine, Daejeon, Korea. kbjoon4u@hananet.net
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Apoptosis;
Exendin-4;
Glucagon-Like Peptide 1;
Oxidative Stress;
Insulin-Secreting Cells
- MeSH:
Animals;
*Apoptosis;
Caspase 3/metabolism;
Caspase 9/metabolism;
Cells, Cultured;
Cricetinae;
Flow Cytometry;
Glucagon-Like Peptide 1/pharmacology;
Glycogen Synthase Kinase 3/*metabolism;
Humans;
Hydrogen Peroxide/toxicity;
Insulin/genetics/metabolism;
Insulin-Secreting Cells/drug effects/*enzymology/metabolism;
JNK Mitogen-Activated Protein Kinases/*metabolism;
*Oxidative Stress;
Peptides/*pharmacology;
Phosphorylation;
Receptors, Glucagon/agonists/metabolism;
Signal Transduction;
Venoms/*pharmacology
- From:Journal of Korean Medical Science
2010;25(11):1626-1632
- CountryRepublic of Korea
- Language:English
-
Abstract:
Oxidative stress induced by chronic hyperglycemia in type 2 diabetes plays a crucial role in progressive loss of beta-cell mass through beta-cell apoptosis. Glucagon like peptide-1 (GLP-1) has effects on preservation of beta-cell mass and its insulin secretory function. GLP-1 possibly increases islet cell mass through stimulated proliferation from beta-cell and differentiation to beta-cell from progenitor cells. Also, it probably has an antiapoptotic effect on beta-cell, but detailed mechanisms are not proven. Therefore, we examined the protective mechanism of GLP-1 in beta-cell after induction of oxidative stress. The cell apoptosis decreased to ~50% when cells were treated with 100 microM H2O2 for up to 2 hr. After pretreatment of Ex-4, GLP-1 receptor agonist, flow cytometric analysis shows 41.7% reduction of beta-cell apoptosis. This data suggested that pretreatment of Ex-4 protect from oxidative stress-induced apoptosis. Also, Ex-4 treatment decreased GSK3beta activation, JNK phosphorylation and caspase-9, -3 activation and recovered the expression of insulin2 mRNA in beta-cell lines and secretion of insulin in human islet. These results suggest that Ex-4 may protect beta-cell apoptosis by blocking the JNK and GSK3beta mediated apoptotic pathway.
