当前位置： SCI文献检索 > JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION期刊下所有文献 > Exendin-4 protects murine MIN6 pancreatic β-cells from interleukin-1β-induced apoptosis via the NF-κB pathway.

Exendin-4 protects murine MIN6 pancreatic β-cells from interleukin-1β-induced apoptosis via the NF-κB pathway.

Abstract：

BACKGROUND:Glucagon-like peptide-1 (GLP-1) and its potent analog, exendin-4, are well known to inhibit β- cell apoptosis and promote β-cell proliferation. Meanwhile, cytokines, such as interleukin-1β (IL-1β), stimulate inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction leading to β-cell damage. However, the protective mechanisms of GLP-1 in β-cells exposed to cytokines have not been fully elucidated. AIMS:In this study, the protective effects of exendin-4 on IL-1β-induced apoptosis were investigated in murine MIN6 pancreatic β-cells. The role of nuclear factor-κB (NF-κB) signaling in this process was also explored. METHODS:The effects of exendin-4 pre-treatment on IL-1β-induced apoptosis were investigated by Hoechst/PI and Annexin V/PI staining. Levels of iNOS and NF-κB proteins were investigated by Western blotting and cytoplasmic nitrite levels were determined using Griess reagent. RESULTS:IL-1β treatment (range, 5-40 ng/ml) for 24 h was positively correlated with nitrite production (R2=0.9668, p<0.01), a significant increase in the percentage of apoptotic cells (p<0.01) and a concomitant dose-dependent increase in cytoplasmic levels of iNOS and NF-κB p65 activation. N-acetyl- L-cysteine (NAC), NG-nitro-L-arginine methyl ester (L-NAME) and pyrrolidine dithiocarbamate (PDTC), partially rescued apoptotic β-cells, suggesting involvement of NF-κB-iNOS-nitrite in this process. Exendin-4 (100 nM) treatment significantly decreased IL-1β-induced apoptosis (p<0.01), downregulated NF-κB activation and subsequently decreased iNOS and nitrite levels in IL-1β-induced β-cells (p<0.001), in a similar manner to L-NAME, PDTC and NAC. CONCLUSIONS:These results suggest that exendin-4 protects against IL-1β- induced apoptosis in β-cells via downregulation of the NF- κB-iNOS-nitrite pathway.

journal_name

J Endocrinol Invest

journal_title

Journal of endocrinological investigation

authors

Liu XH,Wang YP,Wang LX,Chen Z,Liu XY,Liu LB

doi

10.3275/8938

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

803-11

issue

eissn

0391-4097

issn

1720-8386

pii

8938

journal_volume

pub_type

杂志文章

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Exendin-4 protects murine MIN6 pancreatic β-cells from interleukin-1β-induced apoptosis via the NF-κB pathway.