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Mol Cell Biochem ; 452(1-2): 83-94, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30022448

RESUMO

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.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Células Secretoras de Insulina/patologia , Insulinoma/patologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/farmacologia , Silibina/farmacologia , Agonistas dos Receptores da Amilina/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Células Secretoras de Insulina/metabolismo , Insulinoma/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Ratos , Transdução de Sinais , Ativação Transcricional , Células Tumorais Cultivadas , Regulação para Cima
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