Silibinin ameliorates amylin-induced pancreatic ß-cell apoptosis partly via upregulation of GLP-1R/PKA pathway.
Mol Cell Biochem
; 452(1-2): 83-94, 2019 Feb.
Article
em En
| MEDLINE
| ID: mdl-30022448
ABSTRACT
The objective was to investigate the mechanism of the protective effect of silibinin on amylin/Aß1-42-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/Aß1-42 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, Aß1-42-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 Aß1-42 is independent of GLP-1R/PKA pathway.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Apoptose
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Proteínas Quinases Dependentes de AMP Cíclico
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Células Secretoras de Insulina
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Polipeptídeo Amiloide das Ilhotas Pancreáticas
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Receptor do Peptídeo Semelhante ao Glucagon 1
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Silibina
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Insulinoma
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article