葡萄籽原花青素提取物（Grape seed proanthocyanidin extracts，GSPE）在肠道水平上相互作用，增强了胰高血糖素样肽-1（GLP-1）和肽YY（peptide YY，PYY）的释放，从而调节食欲和葡萄糖体内稳态。因此，增加L细胞数量可能是促进激素分泌的策略，这可为肥胖和2型糖尿病（T2DM）的治疗提供一种潜在策略。
Methods & Results
小鼠回肠类器官被用来评估GSPE及其两个主要成分（表儿茶素 （gallic acid，GA）、没食子酸（epicatechin，EC））对肠道分化的长期影响。使用RIA和ELISA试剂盒测定激素水平，并通过实时荧光定量PCR技术(Real-time qPCR)评估参与肠道细胞分化的转录因子的基因表达以及不同细胞类型的标志物。GSPE上调肠激素基因的表达和含量，以及泛内分泌标记物嗜铬粒蛋白A（ChgA）。GSPE还调节了参与L细胞分化的早期和晚期转录因子的时间序列基因表达谱。此外，GSPE上调了杯状细胞（Muc2）和肠上皮细胞（sucraseisomaltase）标志物，同时下调干细胞标志物（Lgr5+）。尽管表儿茶素和没食子酸修饰了肠激素的释放，但它们并未复制GSPE对转录因子谱的作用。
Conclusions
这项研究显示了GSPE在促进肠内分泌分化中的潜在作用，这种作用不是由表儿茶素或没食子酸介导的。
Abstract
Long Term Exposure to a Grape Seed Proanthocyanidin Extract Enhances L‐Cell Differentiation in Intestinal Organoids
àngela Casanova‐Martí, Noemi González‐Abuín, Joan Serrano, M Teresa Blay, Ximena Terra, Gary Frost, Montserrat Pinent, Anna Ardévol
MoBioFood Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, C/Marcel·li Domingo 1, Tarragona, 43007 Spain
Scope
A grape‐seed proanthocyanidin extract (GSPE) interacts at the intestinal level, enhancing glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY) release, which modulate appetite and glucose homeostasis. Thus, enhancing L‐cell numbers could be a strategy to promote hormone production, providing a potential strategy for obesity and type‐2 diabetes mellitus (T2DM) treatment.
Methods and results
Mice ileum organoids are used to evaluate the long‐term effects of GSPE and two of its main components, epicatechin (EC) and gallic acid (GA), on intestinal differentiation. Hormone levels are determined using RIA and ELISA kits, and gene expression of transcription factors involved in intestinal cell differentiation, as well as markers of different cell types, are assessed by real‐time qPCR. GSPE upregulates enterohormone gene expression and content, as well as the pan‐endocrine marker chromogranin A. GSPE also modulates the temporal gene expression profile of early and late transcription factors involved in L‐cell differentiation. Furthermore, GSPE upregulates goblet cell (Muc2) and enterocyte (sucraseisomaltase) markers, while downregulating stem cell markers (Lgr5+). Although EC and GA modified enterohormone release, they do not reproduce GSPE effects on transcription factor’s profile.
Conclusions
This study shows the potential role of GSPE in promoting enteroendocrine differentiation, effect that is not mediated by EC or GA.
