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Mol Cell Biochem. 2019 Feb;452(1-2):83-94. doi: 10.1007/s11010-018-3414-9. Epub 2018 Jul 18.

Silibinin ameliorates amylin-induced pancreatic β-cell apoptosis partly via upregulation of GLP-1R/PKA pathway.

Author information

1
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, People's Republic of China.
2
Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, 2665-1, Nakanomachi, Hachioji, Tokyo, 192-0015, Japan.
3
Nippi Research Institute of Biomatrix, Toride, Ibaraki, 302-0017, Japan.
4
Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo, 194-8543, Japan.
5
Department of Medical Education and Primary Care, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
6
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, People's Republic of China. ikejimat@vip.sina.com.

Abstract

The objective was to investigate the mechanism of the protective effect of silibinin on amylin/Aβ1-42-induced INS-1 cell apoptosis, with special reference to the roles of glucagon-like peptide-1 receptor (GLP-1R) and protein kinase A (PKA). The effects of silibinin on apoptosis, insulin secretion, GLP-1R, and PKA expression in the INS-1 cells treated with amylin/Aβ1-42 were examined. INS-1 cells exposed to amylin showed increased TUNEL-positive ratio, reduced expression of GLP-1R and PKA. GLP-1R antagonists or PKA inhibitor enhanced the expression of apoptosis-associated proteins and TUNEL-positive ratio. Silibinin exerted antiapoptotic effect on and upregulation of GLP-1R and PKA. However, Aβ1-42-induced INS-1 cell apoptosis, GLP-1R, and PKA expressions were not changed. Our results indicate that down-regulation of GLP-1R and PKA contributes to INS-1 cell apoptosis induced with amylin. Silibinin protects INS-1 cells from amylin-induced apoptosis through activation of GLP-1R/PKA signaling. Silibinin's inhibition of the toxic effects of Aβ1-42 is independent of GLP-1R/PKA pathway.

KEYWORDS:

Apoptosis; GLP-1R; INS-1 cells; PKA; Silibinin

PMID:
30022448
DOI:
10.1007/s11010-018-3414-9
[Indexed for MEDLINE]

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