Abstract
To investigate the anti-diabetic properties of chebulic acid (CA) associated with the prevention of methyl glyoxal (MG)-induced mitochondrial dysfunction in INS-1 pancreatic β-cells, INS-1 cells were pre-treated with CA (0.5, 1.0, and 2.0 μM) for 48 h and then treated with 2 mM MG for 8 h. The effects of CA and MG on INS-1 cells were evaluated using the following: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; glyoxalase 1 (Glo-1) expression via Western blot and enzyme activity assays; Nrf-2, nuclear factor erythroid 2-related factor 2 protein expression via Western blot assay; reactive oxygen species (ROS) production assay; mRNA expression of mitochondrial dysfunction related components (UCP2, uncoupling protein 2; VDAC1, voltage-dependent anion-selective channel-1; cyt c, cytochrome c via quantitative reverse transcriptase-PCR; mitochondrial membrane potential (MMP); adenosine triphosphate (ATP) synthesis; glucose-stimulated insulin secretion (GSIS) assay. The viability of INS-1 cells was maintained upon pre-treating with CA before exposure to MG. CA upregulated Glo-1 protein expression and enzyme activity in INS-1 cells and prevented MG-induced ROS production. Mitochondrial dysfunction was alleviated by CA pretreatment; this occurred via the downregulation of UCP2, VDAC1, and cyt c mRNA expression and the increase of MMP and ATP synthesis. Further, CA pre-treatment promoted the recovery from MG-induced decrease in GSIS. These results indicated that CA could be employed as a therapeutic agent in diabetes due to its ability to prevent MG-induced development of insulin sensitivity and oxidative stress-induced dysfunction of β-cells.
Highlights
Diabetes mellitus is a serious chronic metabolic illness with increasing global incidence that presents a major public health concern
We investigated the effect of MG on the mRNA expression of mitochondrial proteins, including uncoupling protein 2 (UCP2), voltage-dependent anion-selective channel protein-1 (VDAC1), and uncoupling protein 2 (UCP2), voltage-dependent anion-selective channel protein-1 (VDAC1), and cytochrome c
We identified the preventive effects of Chebulic Acid (CA) against MG-induced mitochondrial dysfunction in INS-1 pancreatic β-cells
Summary
Diabetes mellitus is a serious chronic metabolic illness with increasing global incidence that presents a major public health concern. According to the 2016 survey of the WHO, 8.5% of the adult population suffers from diabetes, and this incidence is rapidly increasing [1]. Methylglyoxal (MG) is a reactive dicarbonyl compound formed during glycolysis. It is produced during conditions of dicarbonyl stress and is a precursor of advanced glycation end products (AGEs), which trigger aging [3]. The glyoxalase system is a MG detoxification system that is present in the cytosol of all mammalian cells [5]. It is comprised of glyoxalase-1 (Glo-1), Glo-2, and reduced glutathione (GSH).
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