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Silibinin ameliorates amylin-induced pancreatic β-cell apoptosis partly via upregulation of GLP-1R/PKA pathway.
- Source :
-
Molecular and cellular biochemistry [Mol Cell Biochem] 2019 Feb; Vol. 452 (1-2), pp. 83-94. Date of Electronic Publication: 2018 Jul 18. - Publication Year :
- 2019
-
Abstract
- The objective was to investigate the mechanism of the protective effect of silibinin on amylin/Aβ <subscript>1-42</subscript> -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/Aβ <subscript>1-42</subscript>  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, Aβ <subscript>1-42</subscript> -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 Aβ <subscript>1-42</subscript> is independent of GLP-1R/PKA pathway.
- Subjects :
- Amylin Receptor Agonists pharmacology
Animals
Antineoplastic Agents, Phytogenic pharmacology
Insulin-Secreting Cells metabolism
Insulinoma metabolism
Pancreatic Neoplasms metabolism
Pancreatic Neoplasms pathology
Rats
Signal Transduction
Transcriptional Activation
Tumor Cells, Cultured
Up-Regulation
Apoptosis drug effects
Cyclic AMP-Dependent Protein Kinases metabolism
Glucagon-Like Peptide-1 Receptor metabolism
Insulin-Secreting Cells pathology
Insulinoma pathology
Islet Amyloid Polypeptide pharmacology
Silybin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4919
- Volume :
- 452
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30022448
- Full Text :
- https://doi.org/10.1007/s11010-018-3414-9