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KMID : 1204320070230040459
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Laboratory Animal Research
2007 Volume.23 No. 4 p.459 ~ p.464
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Protective Effects of Exendin-4 on Nitric Oxide-Mediated Cell Death in Insulin-Producing RINm5F Cells
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Lee Myoung-Won
Sim Yun-Beom
Kwon Hyeok-Yil
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Abstract
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Exendin-4 derived from the venom of the Gila monster lizard (Heloderma suspectum) shows structural relationship to the important incretin hormone, glucagon like peptide-1. In addition to stimulating insulin secretion, exendin-4 has also been known to stimulate β-cell proliferation and islet mass increase. Although these beneficial effects on diabetes have been suggested, it has not yet been examined the effects of exendin-4 on β-cell destruction by harmful stimuli such as cytokines and reactive radicals. The aim of this study was to investigate whether exendin-4 would confer resistance to the cytotoxic effects of nitric oxide (NO), preserving the viability of rat insulinoma RINm5F cells. Exposure of RINm5F cells to sodium nitroprusside (SNP), an intracellular NO generator, decreased cell viability denoted by MTT and FACS analysis. The intracellular level of superoxide radical and a product of lipid peroxidation, malondialdehyde (MDA) were significantly increased by treatment of SNP for 12 hours. Exendin-4 increased RINm5F cellular viability and markedly attenuated SNP-induced cell death in a dose-dependent manner. The SNP-induced NO and superoxide radical production, MDA production and DNA damage were also significantly decreased by pretreatment of exendin-4. Thus, our results suggest that exendin-4 has protective effects against NO-induced cell death via inhibiting detrimental reactive radical production in insulin-producing RINm5F cells.
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KEYWORD
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Exendin-4, β-cell death, diabetes, NO, superoxide radical
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