title: Flavonoids protect pancreatic beta-cells from cytokines mediated apoptosis through the activation of PI3-kinase pathway.
abstract: The preventive effects of four phenolic compounds against cytokines-induced β-cell destruction were assessed in this study. Treatment of INS-1 (832/13) cells with pro-inflammatory cytokine mixtures (interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)) resulted in an increased apoptosis. While resveratrol or myricetin failed to prevent cell apoptosis, quercetin or naringenin treatment exhibited an about 40% less in cell death induced by cytokines-mediated damage. This protective effect of quercetin or naringenin might be mediated partially via the activation of the downstream pAkt and pBad pathways, an outcome which was abolished by pretreatment with a specific PI3-kinase inhibitor. Cellular protein levels of p-p38 MAPK and inducible NO synthase (iNOS) were enhanced after cytokines addition; however, the presence of quercetin or naringenin could not suppress their expression. While cytokines induced MnSOD, quercetin or naringnin did not further enhance expression of this protective protein. In addition, the loss of mitochondria membrane potential (MMP) after cytokines treatment might be partially corrected with quercetin or naringenin. However, none of the phenolic compounds tested in this study reversed the blunted glucose-stimulated insulin secretion after cytokines treatment. These results suggest that quercetin or naringenin might possibly be able to protect β-cells from cytokines toxicity by enhancing cell survival through PI3-kinase pathway, independent of p-p38 MAPK or iNOS.
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan. clin@asia.edu.tw
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Chih-Chin
authors.initials: CC
authors.lastname: Ni
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Yin
authors.forename: Chong-Kuei
authors.initials: CK
authors.lastname: Lii
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000633:toxicity*; D019610:Cytoprotection / Q000187:drug effects*; D003720:Densitometry; D004789:Enzyme Activation / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D044950:Flavanones; D005419:Flavonoids; D007328:Insulin; D010636:Phenols; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D056564:Sirtuin 1; C005273:naringenin; D005947:Glucose