Gallic acid protects RINm5F β‐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.

In Vivo and In Vitro Antidiabetic Activity of Terminalia paniculata Bark: An Evaluation of Possible Phytoconstituents and Mechanisms for Blood Glucose Control in Diabetes

“…The GA, isolated from Terminalia bellerica fruit, treatment in diabetic rats showed significant antidiabetic activity [27]. GA-mediated glucose transporter 4 (GLUT4) translocation, glucose uptake in adipocyte cells, and insulin secretagogue actions in pancreatic cells were reported [28, 29]. In present study, insulin sensitization assay, incubation of AETPB and GA enhances glucose uptake in skeletal muscle cells which confirmed that GA possibly mediate the antidiabetic activity of AETPB.…”

Antidiabetic Compounds in Syzygium cumini Decoction and Ready to Serve Herbal Drink

“…Several studies have proven the significant antidiabetic effects and cardioprotective effects of gallic acid. Gallic acid increases GLUT4 translocation and cellular glucose uptake [16] prevents diabetes-induced cardiac dysfunction and causes significant decrease in the malonaldehyde, an indicator of lipid peroxidation in STZ-diabetic rats [17], and protects RINm5F beta-cells from glucolipotoxicity by its antiapoptotic and insulin-secretagogue actions [18]. Umbelliferone (UMB), also known as 7-hydroxycoumarin, hydrangine, skimmetine, and beta-umbelliferone, belongs to the coumarin family.…”

Complexing of Green Tea Catechins with Food Constituents and Degradation of the Complexes by <i>Lactobacillus plantarum</i>

“…Furthermore, non-galloyl ester catechins and GA were found to have marked antioxidant effects, which may exert synergistically beneficial health effects to ameliorate metabolic diseases such as diabetes mellitus [33]. In this context, the present findings lead us to propose that a greater population of the L. plantarum strain with high tannase activity would degrade macromolecular complexes of catechin galloyl esters and dietary proteins to release more non-galloyl ester catechins and GA in the human host intestine.…”