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KMID : 0191120100250111626
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Journal of Korean Medical Science
2010 Volume.25 No. 11 p.1626 ~ p.1632
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Exendin-4 Protects Oxidative Stress-Induced β-Cell Apoptosis through Reduced JNK and GSK3β Activity
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Kim Ju-Young
Lim Dong-Mee
Moon Chan-Il
Jo Kyung-Jin
Lee Seong-Kyu
Baik Haing-Woon
Lee Ki-Ho
Lee Kang-Woo
Park Keun-Young
Kim Byung-Joon
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Abstract
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Oxidative stress induced by chronic hyperglycemia in type 2 diabetes plays a crucial role in progressive loss of β-cell mass through β-cell apoptosis. Glucagon like peptide-1 (GLP-1) has effects on preservation of β-cell mass and its insulin secretory function. GLP-1 possibly increases islet cell mass through stimulated proliferation from β-cell and differentiation to β-cell from progenitor cells. Also, it probably has an antiapoptotic effect on β-cell, but detailed mechanisms are not proven. Therefore, we examined the protective mechanism of GLP-1 in β-cell after induction of oxidative stress. The cell apoptosis decreased to ~50% when cells were treated with 100 μM H2O2 for up to 2 hr. After pretreatment of Ex-4, GLP-1 receptor agonist, flow cytometric analysis shows 41.7% reduction of β-cell apoptosis. This data suggested that pretreatment of Ex-4 protect from oxidative stress-induced apoptosis. Also, Ex-4 treatment decreased GSK3β activation, JNK phosphorylation and caspase-9, -3 activation and recovered the expression of insulin2 mRNA in β-cell lines and secretion of insulin in human islet. These results suggest that Ex-4 may protect β-cell apoptosis by blocking the JNK and GSK3β mediated apoptotic pathway.
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KEYWORD
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Apoptosis, Exendin-4, Glucagon-Like Peptide 1, Oxidative Stress, Insulin-Secreting Cells
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