Exendin-4 Protects Oxidative Stress-Induced beta-Cell Apoptosis through Reduced JNK and GSK3beta Activity
Journal of Korean Medical Science
;
: 1626-1632, 2010.
Article
in English
| WPRIM
| ID: wpr-44279
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Peptides
/
Phosphorylation
/
Venoms
/
Signal Transduction
/
Cells, Cultured
/
Apoptosis
/
Receptors, Glucagon
/
Oxidative Stress
/
Glycogen Synthase Kinase 3
/
JNK Mitogen-Activated Protein Kinases
Limits:
Animals
/
Humans
Language:
English
Journal:
Journal of Korean Medical Science
Year:
2010
Type:
Article
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