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ι-Carrageenan Tetrasaccharide from ι-Carrageenan Inhibits Islet β Cell Apoptosis Via the Upregulation of GLP-1 to Inhibit the Mitochondrial Apoptosis Pathway
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2020-12-22 , DOI: 10.1021/acs.jafc.0c06456 Yanqi Li 1 , Yanchao Wang 1 , Lei Zhang 1 , Ziyi Yan 1 , Jingjing Shen 1 , Yaoguang Chang 1 , Jingfeng Wang 1
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2020-12-22 , DOI: 10.1021/acs.jafc.0c06456 Yanqi Li 1 , Yanchao Wang 1 , Lei Zhang 1 , Ziyi Yan 1 , Jingjing Shen 1 , Yaoguang Chang 1 , Jingfeng Wang 1
Affiliation
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ι-Carrageenan performs diversified biological activities but has low bioavailability. ι-Carrageenan tetrasaccharide (ιCTs), a novel marine oligosaccharide prepared by the marine enzyme Cgi82A, was investigated for its effects on insulin resistance in high-fat and high-sucrose diet mice. Oral administration of ιCTs (ιCTs-L 30.0 mg/kg·bw, ιCTs-H 90.0 mg/kg·bw) decreased fasting blood glucose by 35.1% ± 1.41 (P < 0.01) and 27.4% ± 0.420 (P < 0.05), and enhanced glucose tolerance. Besides, ιCTs-L ameliorated islet vacuolization, decreased the β cell apoptosis by 21.8% ± 0.200 (P < 0.05), and promoted insulin secretion by 5.41% ± 0.0173 (P < 0.01) through pancreatic hematoxylin and eosin (H&E) staining, TUNEL staining, and insulin–glucagon immunostaining analysis. Interestingly, ιCTs-L and ιCTs-H treatment increased the incretin GLP-1 content in serum by 22.1% ± 0.402 (P < 0.01) and 10.7% ± 0.0935 (P < 0.05) respectively, through regulating the bile acid levels, which contributed to the inhibition of β cell apoptosis. Mechanically, ιCTs upregulated the expression of the GLP-1 receptor (GLP-1R) and protein kinase A (PKA) in the GLP-1/cAMP/PKA signaling pathway, and further inhibited the expression of cytochrome C and caspase 3 in the mitochondrial apoptotic pathway. In conclusion, this study suggested that ιCTs alleviated insulin resistance by GLP-1-mediated inhibition of β cell apoptosis and proposed a new strategy for developing potential functional foods that prevent insulin resistance.
中文翻译：
来自α-角叉菜胶的α-角叉菜胶四糖通过上调GLP-1抑制线粒体细胞凋亡途径抑制胰岛β细胞凋亡。
角叉菜胶具有多种生物活性，但生物利用度低。研究了通过海洋酶Cgi82A制备的新型海洋寡糖α-角叉菜胶四糖（ICT）对高脂和高蔗糖饮食小鼠中胰岛素抵抗的影响。口服iCTs（iCTs-L 30.0 mg / kg·bw，ηCTs-H90.0 mg / kg·bw）可使空腹血糖降低35.1％±1.41（P <0.01）和27.4％±0.420（P <0.05），和增强的葡萄糖耐量。此外，ÄCTs-L改善了胰岛的空泡形成，使β细胞凋亡减少了21.8％±0.200（P <0.05），并促进了胰岛素分泌，增加了5.41％±0.0173（P<0.01）通过胰腺苏木和曙红（H＆E）染色，TUNEL染色以及胰岛素-胰高血糖素免疫染色分析。有趣的是，通过调节胆汁酸水平，ÄCTs-L和ÄCTs-H处理分别使血清中肠降血糖素GLP-1含量增加了22.1％±0.402（P <0.01）和10.7％±0.0935（P <0.05）。抑制β细胞凋亡。在机械上，ιCTs上调GLP-1 / cAMP / PKA信号通路中GLP-1受体（GLP-1R）和蛋白激酶A（PKA）的表达，并进一步抑制细胞色素C的表达线粒体凋亡途径中的半胱氨酸蛋白酶和半胱天冬酶3。总而言之，这项研究表明，iCTs通过GLP-1介导的β细胞凋亡抑制作用减轻了胰岛素抵抗，并提出了开发潜在的预防胰岛素抵抗功能食品的新策略。
更新日期：2021-01-13
中文翻译：
来自α-角叉菜胶的α-角叉菜胶四糖通过上调GLP-1抑制线粒体细胞凋亡途径抑制胰岛β细胞凋亡。
角叉菜胶具有多种生物活性，但生物利用度低。研究了通过海洋酶Cgi82A制备的新型海洋寡糖α-角叉菜胶四糖（ICT）对高脂和高蔗糖饮食小鼠中胰岛素抵抗的影响。口服iCTs（iCTs-L 30.0 mg / kg·bw，ηCTs-H90.0 mg / kg·bw）可使空腹血糖降低35.1％±1.41（P <0.01）和27.4％±0.420（P <0.05），和增强的葡萄糖耐量。此外，ÄCTs-L改善了胰岛的空泡形成，使β细胞凋亡减少了21.8％±0.200（P <0.05），并促进了胰岛素分泌，增加了5.41％±0.0173（P<0.01）通过胰腺苏木和曙红（H＆E）染色，TUNEL染色以及胰岛素-胰高血糖素免疫染色分析。有趣的是，通过调节胆汁酸水平，ÄCTs-L和ÄCTs-H处理分别使血清中肠降血糖素GLP-1含量增加了22.1％±0.402（P <0.01）和10.7％±0.0935（P <0.05）。抑制β细胞凋亡。在机械上，ιCTs上调GLP-1 / cAMP / PKA信号通路中GLP-1受体（GLP-1R）和蛋白激酶A（PKA）的表达，并进一步抑制细胞色素C的表达线粒体凋亡途径中的半胱氨酸蛋白酶和半胱天冬酶3。总而言之，这项研究表明，iCTs通过GLP-1介导的β细胞凋亡抑制作用减轻了胰岛素抵抗，并提出了开发潜在的预防胰岛素抵抗功能食品的新策略。
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