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Exendin-4 protects murine MIN6 pancreatic β-cells from interleukin-1β-induced apoptosis via the NF-κB pathway.
J Endocrinol Invest 2013; 36(10):803-11JE

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.

Authors+Show Affiliations

Department of Endocrinology, Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian 350001, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23609920

Citation

Liu, X H., et al. "Exendin-4 Protects Murine MIN6 Pancreatic Β-cells From Interleukin-1β-induced Apoptosis Via the NF-κB Pathway." Journal of Endocrinological Investigation, vol. 36, no. 10, 2013, pp. 803-11.
Liu XH, Wang YP, Wang LX, et al. Exendin-4 protects murine MIN6 pancreatic β-cells from interleukin-1β-induced apoptosis via the NF-κB pathway. J Endocrinol Invest. 2013;36(10):803-11.
Liu, X. H., Wang, Y. P., Wang, L. X., Chen, Z., Liu, X. Y., & Liu, L. B. (2013). Exendin-4 protects murine MIN6 pancreatic β-cells from interleukin-1β-induced apoptosis via the NF-κB pathway. Journal of Endocrinological Investigation, 36(10), pp. 803-11. doi:10.3275/8938.
Liu XH, et al. Exendin-4 Protects Murine MIN6 Pancreatic Β-cells From Interleukin-1β-induced Apoptosis Via the NF-κB Pathway. J Endocrinol Invest. 2013;36(10):803-11. PubMed PMID: 23609920.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exendin-4 protects murine MIN6 pancreatic β-cells from interleukin-1β-induced apoptosis via the NF-κB pathway. AU - Liu,X H, AU - Wang,Y P, AU - Wang,L X, AU - Chen,Z, AU - Liu,X Y, AU - Liu,L B, Y1 - 2013/04/18/ PY - 2013/4/24/entrez PY - 2013/4/24/pubmed PY - 2014/11/14/medline SP - 803 EP - 11 JF - Journal of endocrinological investigation JO - J. Endocrinol. Invest. VL - 36 IS - 10 N2 - 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. SN - 1720-8386 UR - https://www.unboundmedicine.com/medline/citation/23609920/Exendin_4_protects_murine_MIN6_pancreatic_β_cells_from_interleukin_1β_induced_apoptosis_via_the_NF_κB_pathway_ L2 - https://link.springer.com/article/10.3275/8938 DB - PRIME DP - Unbound Medicine ER -