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Autocrine C‐peptide protects INS1 β cells against palmitic acid‐induced oxidative stress in peroxisomes by inducing catalase

机译:通过诱导过氧化氢酶,保护C-肽通过诱导过氧化酶来保护INS1β细胞免受棕榈酸诱导的过氧化物诱导的氧化胁迫

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Aims C‐peptide, produced by pancreatic β cells and co‐secreted in the bloodstream with insulin, has antioxidant properties in glucose‐ and hydrogen peroxide (Hsub2/subOsub2/sub)‐exposed INS1 β cells. Palmitic acid, the most physiologically abundant long‐chain free fatty acid in humans, is metabolized in peroxisomes of β cells accumulating Hsub2/subOsub2/sub that can lead to oxidative stress. Here, we tested the hypothesis that C‐peptide protects β cells from palmitic acid‐induced stress by lowering peroxisomal Hsub2/subOsub2/sub. Materials and methods We exposed INS1 β cells to palmitic acid and C‐peptide in the setting of increasing glucose concentration and tested for changes in parameters of stress and death. To study the ability of C‐peptide to lower peroxisomal Hsub2/subOsub2/sub, we engineered an INS1 β cell line stably expressing the peroxisomal‐targeted Hsub2/subOsub2/sub sensor HyPer, whose fluorescence increases with cellular Hsub2/subOsub2/sub. An INS1 β cell line stably expressing a live‐cell fluorescent catalase reporter was used to detect changes in catalase gene expression. Results C‐peptide protects INS1 β cells from the combined effect of palmitic acid and glucose by reducing peroxisomal Hsub2/subOsub2/sub to baseline levels and increasing expression of catalase. Conclusions In conditions of glucolipotoxicity, C‐peptide increases catalase expression and reduces peroxisomal oxidative stress and death of INS1 β cells. Maintenance of C‐peptide secretion is a pro‐survival requisite for β cells in adverse conditions. Loss of C‐peptide secretion would render β cells more vulnerable to stress and death leading to secretory dysfunction and diabetes.
机译:目的是由胰腺β细胞产生的C-肽,并在血液血液中共分泌,具有葡萄糖和过氧化氢的抗氧化性质(H 2 O 2 ) - 暴露的INS1β细胞。棕榈酸,人类中最生理的丰富的无链条游离脂肪酸,在β细胞的过氧化物中代谢,其累积H 2 O 2 ,其导致氧化应激。在这里,我们测试了C-肽通过降低过氧酶体H 2 -2 2 通过降低过氧异甲酸甲酸诱导的应力保护β细胞的假设。在葡萄糖浓度增加并测试应力和死亡参数的变化中,我们将INS1β细胞暴露于棕榈酸和C-肽中的棕榈酸和C肽。为了研究C-肽对低氧异相体H 2 O 2 的能力,我们设计了稳定地表达过氧酶体靶向H 2的INS1β细胞系 O 2 传感器HEAD,其荧光随蜂窝H 2 O 2 。用于稳定表达活细胞荧光过氧化酶报告的Ins1β细胞系检测过氧化氢酶基因表达的变化。结果C-肽通过将过氧异甲酸异构体H 2 - 2 降至基线水平并增加过氧化氢酶表达来保护INS1β细胞免受棕榈酸和葡萄糖的综合作用。结论在葡糖毒性的条件下,C-肽增加了过氧化氢酶表达并减少过氧异相体氧化应激和INS1β细胞的死亡。维持c-肽分泌是β细胞在不利条件下的β细胞的预存。丧失C-肽分泌将使β细胞更容易受到应激和死亡的影响,导致分泌功能障碍和糖尿病。

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