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

Molecular and Cellular Biochemistry
Jing YangTakashi Ikejima

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.

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Citations

Apr 9, 2020·Frontiers in Molecular Neuroscience·Ana F RaimundoRegina Menezes
Aug 17, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Maryam FallahHamed Mirzaei
Oct 13, 2021·Journal of Cellular Physiology·Carine MarmentiniMirian A Kurauti
Dec 17, 2021·Acta Pharmacologica Sinica·Wei-Wei LiuTakashi Ikejima

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
fluorescence microscopy
electrophoresis

Software Mentioned

Image Pro - Plus
GraphPad Prism

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