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Narrow-leafed lupin (Lupinus angustifolius L.) seed β-conglutins reverse the induced insulin resistance in pancreatic cells†
Food & Function ( IF 5.1 ) Pub Date : 2018-09-10 00:00:00 , DOI: 10.1039/c8fo01164h Elena Lima-Cabello 1, 2, 3, 4, 5 , Sonia Morales-Santana 6, 7, 8, 9, 10 , Josefa León 9, 10, 11, 12, 13 , Victor Alché 5, 14, 15, 16 , Alfonso Clemente 3, 5, 17, 18 , Juan D. Alché 1, 2, 3, 4, 5 , Jose C. Jimenez-Lopez 1, 2, 3, 4, 5
Food & Function ( IF 5.1 ) Pub Date : 2018-09-10 00:00:00 , DOI: 10.1039/c8fo01164h Elena Lima-Cabello 1, 2, 3, 4, 5 , Sonia Morales-Santana 6, 7, 8, 9, 10 , Josefa León 9, 10, 11, 12, 13 , Victor Alché 5, 14, 15, 16 , Alfonso Clemente 3, 5, 17, 18 , Juan D. Alché 1, 2, 3, 4, 5 , Jose C. Jimenez-Lopez 1, 2, 3, 4, 5
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Insulin resistance (IR) is the main contributor to the development of type 2 diabetes. In this study, we have purified recombinant β-conglutin proteins (rβ1 to rβ4, and rβ6) from narrow-leafed lupin (NLL) by using affinity chromatography. The objective of this study was to evaluate the capacity of these β-conglutins to improve the IR state using ex vivo and in vitro systems. rβ1, rβ3, and rβ6 produced lower levels of pro-inflammatory mediator nitric oxide (about -7-fold in all cases), up-regulated mRNA expression levels of IRS-1 (+201, +173, +192%) and Glut-4 (+286, +121, +147%), increased levels of p85-PI3K (+188, +187, +137-fold) and Glut-4 (+503, +548, +515-fold) proteins, higher phosphorylation levels of the insulin signalling pathway activator p-IRS-1 and downstream mediators such as p-Akt, p-Cbl, and p-caveolin, and improved glucose uptake in insulin resistant (IR-C) culture cells. β-conglutin proteins were able to suppress the oxidative stress produced by insulin-induced resistance on PANC-1 control (C) cells by strongly reducing the protein oxidative carbonylation induced by ROS and balancing the metabolic homeostasis in IR-C cells through regulation of mRNA expression. At the same time, β-conglutins are able to reduce the levels of the pro-inflammatory mediator nitric oxide and promote the anti-oxidative capacity of cells by increasing the levels of reduced glutathione. These results suggest NLL β-conglutins might play a fundamental role as functional food components, since β-conglutins’ nutraceutical properties could enhance the effectiveness of dietary improvement of type 2 diabetes complications.
中文翻译：
羽扇豆羽扇豆（Lupinus angustifolius L.）种子β-凝集素可逆转胰腺细胞中诱导的胰岛素抵抗†
胰岛素抵抗（IR）是2型糖尿病发展的主要因素。在这项研究中，我们使用亲和色谱法从窄叶羽扇豆（NLL）中纯化了重组β-凝集素蛋白（rβ1至rβ4和rβ6）。这项研究的目的是评估离体和体外这些β-凝集素改善IR状态的能力系统。rβ1，rβ3和rβ6产生的促炎性一氧化氮水平较低（在所有情况下约为-7倍），IRS-1的mRNA表达水平上调（+ 201，+ 173，+ 192％）和谷胱甘肽-4（+ 286，+ 121，+ 147％），p85-PI3K（+ 188，+ 187，+ 137倍）和Glut-4（+ 503，+ 548，+ 515倍）蛋白水平升高，胰岛素信号通路激活剂p-IRS-1和下游介体（例如p-Akt，p-Cbl和p-小血管紧张素）的磷酸化水平更高，并改善了胰岛素抵抗（IR-C）培养细胞的葡萄糖摄取。β-凝集素蛋白能够通过强烈减少ROS诱导的蛋白质氧化羰基化并通过调节mRNA来平衡IR-C细胞的代谢稳态来抑制胰岛素诱导的对PANC-1对照（C）细胞的抗性所产生的氧化应激表达。同时，β-conglutins能够通过增加还原型谷胱甘肽的水平来降低促炎介质一氧化氮的水平，并促进细胞的抗氧化能力。这些结果表明，NLL-β-凝集素可能起着功能性食品成分的基本作用，因为β-凝集素的营养特性可以增强饮食改善2型糖尿病并发症的有效性。
更新日期：2018-09-10
中文翻译：
羽扇豆羽扇豆（Lupinus angustifolius L.）种子β-凝集素可逆转胰腺细胞中诱导的胰岛素抵抗†
胰岛素抵抗（IR）是2型糖尿病发展的主要因素。在这项研究中，我们使用亲和色谱法从窄叶羽扇豆（NLL）中纯化了重组β-凝集素蛋白（rβ1至rβ4和rβ6）。这项研究的目的是评估离体和体外这些β-凝集素改善IR状态的能力系统。rβ1，rβ3和rβ6产生的促炎性一氧化氮水平较低（在所有情况下约为-7倍），IRS-1的mRNA表达水平上调（+ 201，+ 173，+ 192％）和谷胱甘肽-4（+ 286，+ 121，+ 147％），p85-PI3K（+ 188，+ 187，+ 137倍）和Glut-4（+ 503，+ 548，+ 515倍）蛋白水平升高，胰岛素信号通路激活剂p-IRS-1和下游介体（例如p-Akt，p-Cbl和p-小血管紧张素）的磷酸化水平更高，并改善了胰岛素抵抗（IR-C）培养细胞的葡萄糖摄取。β-凝集素蛋白能够通过强烈减少ROS诱导的蛋白质氧化羰基化并通过调节mRNA来平衡IR-C细胞的代谢稳态来抑制胰岛素诱导的对PANC-1对照（C）细胞的抗性所产生的氧化应激表达。同时，β-conglutins能够通过增加还原型谷胱甘肽的水平来降低促炎介质一氧化氮的水平，并促进细胞的抗氧化能力。这些结果表明，NLL-β-凝集素可能起着功能性食品成分的基本作用，因为β-凝集素的营养特性可以增强饮食改善2型糖尿病并发症的有效性。
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