The effect of FFAR1 on pioglitazone-mediated attenuation of palmitic acid-induced oxidative stress and apoptosis in βTC6 cells
Abstract
We sought to determine whether free fatty acid receptor 1 (FFAR1), a receptor for free fatty acids on the β-cell membrane, can mediate the pioglitazone (PIO)-attenuating effect on lipoapoptosis in β cells and its relationship to oxidative stress. The glucose-sensitive mouse beta pancreatic cell line βTC6 was used to investigate the effect of FFAR1 on PIO-attenuating palmitic acid (PA)-induced oxidative stress and apoptosis. (1) PIO reduced PA-induced lipoapoptosis in β cells and upregulated the expression of FFAR1 at the mRNA and protein levels in a dose- and time-dependent manner. Silencing of FFAR1 expression was shown to weaken the protective effect of PIO on PA-induced lipoapoptosis in βTC6 cells; while lentiviral-mediated overexpression of FFAR1 was shown to enhance the protective effect of PIO against lipoapoptosis in β cells. (2) Downregulation of FFAR1 expression reduced the attenuating effect of PIO on the expression of NAPDH oxidase subunit p47(phox), Bax, cleaved caspase 3, and the production of reactive oxygen specific (ROS) induced by lipotoxicity, thereby preventing the upregulation of the expression of bcl-2. Inducing the overexpression of FFAR1 enhanced the anti-oxidative stress effect of PIO. Similarly, these e...Continue Reading
References
Insulin improves β-cell function in glucose-intolerant rat models induced by feeding a high-fat diet
The association of oxidative stress markers with conventional risk factors in the metabolic syndrome
Citations
Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells.
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