TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway.

Advanced glycation end products (AGEs), which accumulate in the body during the development of diabetes, may be one of the factors leading to pancreatic β-cell failure and reduced β-cell mass. However, the mechanisms responsible for AGE‑induced apoptosis remain unclear. This study identified the role and mechanisms of action of tribbles homolog 3 (TRB3) in AGE-induced β-cell oxidative damage and apoptosis. Rat insulinoma cells (INS-1) were treated with 200 µg/ml AGEs for 48 h, and cell apoptosis was then detected by TUNEL staining and flow cytometry. The level of intracellular reactive oxygen was measured by a fluorescence assay. The expression levels of receptor of TRB3, protein and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) were evaluated by RT-qPCR and western blot analysis. siRNA was used to knockdown TRB3 expression through lipofection, followed by an analysis of the effects of TRB3 on and NOX4. Furthermore, the inhibitor, LY333531, was used to analyze the effects of duanyu1531β2 on levels and apoptosis. We found that AGEs induced the apoptosis of INS-1 cells and upregulated and TRB3 expression. AGEs also increased duanyu1670 levels in β-cells. Following the knockdown of TRB3, the AGE-induced apoptosis and intracellular duanyu1670 levels were significantly decreased, suggesting that TRB3 mediated AGE-induced apoptosis. Further experiments demonstrated that the knockdown of TRB3 decreased the duanyu1531β2 and NOX4 expression levels. When TRB3 was knocked down, the cells expressed decreased levels of duanyu1531β2 and NOX4. The inhibitor, LY333531, also reduced AGE-induced apoptosis and intracellular duanyu1670 levels. Taken together, our data suggest that TRB3 mediates AGE-induced oxidative injury in β-cells through the

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