title: Gallic acid protects RINm5F beta-cells from glucolipotoxicity by its antiapoptotic and insulin-secretagogue actions.
abstract: Gallic acid is claimed to possess antioxidant, antiinflammatory and cytoprotective effects. Since pancreatic islets from Type 2 diabetic patients have functional defects, it was hypothesized that glucolipotoxicity might induce apoptosis in beta-cells and gallic acid could offer protection. To test this, RINm5F beta-cells were exposed to high glucose (25 microM) or palmitate (500 microM) or a combination of both for 24 h in the presence and absence of gallic acid. Cells subjected to glucolipotoxicity in the absence and presence of gallic acid were assessed for DNA damage by comet assay. Apoptosis was inferred by caspase-3 protein expression and caspase-3 activity and changes in Bcl-2 mRNA. RT-PCR was used to analyse PDX-1, insulin and UCP-2 mRNA expression in RINm5F beta-cells and insulin levels were quantified from the cell culture supernatant. NFkappaB signal was studied by EMSA, immunofluorescence and Western blot analysis. While RINm5F beta-cells subjected to glucolipotoxicity exhibited increased DNA damage, apoptotic markers and NFkappaB signals, all these apoptotic perturbations were resisted by gallic acid. Gallic acid dose-dependently increased insulin secretion in RINm5F beta-cells and upregulated mRNA of PDX-1 and insulin. It is suggested that the insulin-secretagogue and transcriptional regulatory action of gallic acid is a newly identified mechanism in our study.
authors.affiliation: Department of Cell and Molecular Biology, Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India 600086.
authors.forename: Zaheer
authors.initials: Z
authors.lastname: Sameermahmood
authors.forename: Lenin
authors.initials: L
authors.lastname: Raji
authors.forename: Thangavel
authors.initials: T
authors.lastname: Saravanan
authors.forename: Ashok
authors.initials: A
authors.lastname: Vaidya
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.forename: Muthuswamy
authors.initials: M
authors.lastname: Balasubramanyam
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004249:DNA Damage; D024202:Electrophoretic Mobility Shift Assay; D005707:Gallic Acid / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005947:Glucose / Q000009:adverse effects; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D007473:Ion Channels / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019308:Palmitic Acid / Q000009:adverse effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; C084010:pancreatic and duodenal homeobox 1 protein; D019308:Palmitic Acid; D005707:Gallic Acid; D053148:Caspase 3; D005947:Glucose