Nutrigenomics Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Marcel·lí Domingo s/n, 43007 Tarragona, Spain.
J Nutr Biochem. 2013 Jun;24(6):948-53. doi: 10.1016/j.jnutbio.2012.06.015. Epub 2012 Sep 17.
Procyanidins have positive effects on glucose metabolism in conditions involving slightly disrupted glucose homeostasis, but it is not clear how procyanidins interact with β-cells. In this work, we evaluate the effects of procyanidins on β-cell functionality under an insulin-resistance condition. After 13 weeks of cafeteria diet, female Wistar rats were treated with 25 mg of grape seed procyanidin extract (GSPE)/kg of body weight (BW) for 30 days. To determine the possible mechanisms of action of procyanidins, INS-1E cells were separately incubated in high-glucose, high-insulin and high-oleate media to reproduce the conditions the β-cells were subjected to during the cafeteria diet feeding. In vivo experiments showed that chronic GSPE treatment decreased insulin production, since C-peptide levels and insulin protein levels in plasma were lower than those of cafeteria-fed rats, as were insulin and Pdx1 mRNA levels in the pancreas. GSPE effects observed in vivo were reproduced in INS-1E cells cultured with high oleate for 3 days. GSPE treatment significantly reduces triglyceride content in β-cells treated with high oleate and in the pancreas of cafeteria-fed rats. Moreover, gene expression analysis of the pancreas of cafeteria-fed rats revealed that procyanidins up-regulated the expression of Cpt1a and down-regulated the expression of lipid synthesis-related genes such as Fasn and Srebf1. Procyanidin treatment counteracted the decrease of AMPK protein levels after cafeteria treatment. Procyanidins cause a lack of triglyceride accumulation in β-cells. This counteracts its negative effects on insulin production, allowing for healthy levels of insulin production under hyperlipidemic conditions.
原花青素对葡萄糖稳态略有失调的情况下的葡萄糖代谢有积极影响，但原花青素与β细胞如何相互作用尚不清楚。在这项工作中，我们评估了胰岛素抵抗条件下原花青素对β细胞功能的影响。经过 13 周的 cafeteria 饮食后，雌性 Wistar 大鼠用 25mg/kg 的葡萄籽原花青素提取物（GSPE）处理 30 天。为了确定原花青素的可能作用机制，将 INS-1E 细胞分别在高葡萄糖、高胰岛素和高油酸培养基中孵育，以重现β细胞在 cafeteria 饮食喂养期间所经历的条件。体内实验表明，慢性 GSPE 处理降低了胰岛素的产生，因为血浆中 C 肽水平和胰岛素蛋白水平低于 cafeteria 喂养大鼠，而胰腺中的胰岛素和 Pdx1mRNA 水平也低于 cafeteria 喂养大鼠。在体外培养 3 天的高油酸处理的 INS-1E 细胞中重现了 GSPE 在体内观察到的作用。GSPE 处理显著降低了高油酸处理的β细胞和 cafeteria 喂养大鼠胰腺中的甘油三酯含量。此外，对 cafeteria 喂养大鼠胰腺的基因表达分析表明，原花青素上调了 Cpt1a 的表达，并下调了脂肪酸合成相关基因如 Fasn 和 Srebf1 的表达。原花青素处理可逆转 cafeteria 处理后 AMPK 蛋白水平的下降。原花青素导致β细胞中甘油三酯积累不足。这抵消了它对胰岛素产生的负面影响，使在高脂血症条件下也能保持健康的胰岛素产生水平。
