(-)-表儿茶素和花色苷调节 GLP-1 代谢：来自 C57BL/6J 小鼠和 GLUTag 细胞的证据。
(-)-Epicatechin and Anthocyanins Modulate GLP-1 Metabolism: Evidence from C57BL/6J Mice and GLUTag Cells.
机构信息
Department of Nutrition and of Environmental Toxicology, University of California, Davis, CA, USA.
Pharmanex Research, NuSkin Enterprise Products, Inc., Provo, UT, USA.
出版信息
J Nutr. 2021 Jun 1;151(6):1497-1506. doi: 10.1093/jn/nxab029.
BACKGROUND
Generated in intestinal L cells through cleavage of proglucagon (Gcg), glucagon-like peptide 1 (GLP-1) is secreted and rapidly inactivated by dipeptidyl peptidase IV (DPP-IV). GLP-1 regulates insulin secretion and overall glucose homeostasis. The capacity of dietary bioactives to increase GLP-1 circulating levels, and therefore increase insulin secretion and glucose metabolism, has gained significant interest of late.
OBJECTIVES
We evaluated the effects of (-)-epicatechin (EC) and different anthocyanins (ACs) and AC metabolites on GLP-1 metabolism in mice and on GLUTag cells.
METHODS
We fed 6-week-old C57BL/6J male mice a control diet or a control diet supplemented with either 40 mg AC or 20 mg EC/kg body weight for 14 weeks (AC) or 15 weeks (EC). Intestinal mRNA levels of Gcg and Dpp-iv were measured. In vitro, GLUTag cells were incubated in the presence or absence of different ACs, the AC metabolite protocatechuic acid (PCA), and EC. GLP-1 secretion and the main pathways involved in its release were assessed.
RESULTS
Long-term supplementation with EC or AC increased mouse GLP-1 plasma concentrations (55% and 98%, respectively; P < 0.05). In mice, 1) EC and AC increased Gcg mRNA levels in the ileum (91%) and colon (41%), respectively (P < 0.05); and 2) AC lowered ileum Dpp-iv mRNA levels (35%), while EC decreased plasma DPP-IV activity (15%; P < 0.05). In GLUTag cells, 1) cyanidin, delphinidin, PCA, and EC increased GLP-1 secretion (53%, 33%, 53%, and 68%, respectively; P < 0.05); and 2) cyanidin, delphinidin, EC, and PCA increased cyclin adenosine monophosphate levels (25-50%; P < 0.05) and activated protein kinase A (PKA; 100%, 50%, 80%, and 86%, respectively; P < 0.05).
CONCLUSIONS
In mice, EC and ACs regulated different steps in GLP-1 regulation, leading to increased plasma GLP-1. Cyanidin, delphinidin, PCA, and EC promoted GLP-1 secretion from GLUTag cells by activating the PKA-dependent pathway. These findings support the beneficial actions of these flavonoids in sustaining intestinal and glucose homeostasis through the modulation of the GLP-1 metabolism.
背景
胰高血糖素原（Gcg）在肠道 L 细胞中被切割产生胰高血糖素样肽 1（GLP-1），它被迅速分泌并被二肽基肽酶 IV（DPP-IV）灭活。GLP-1 调节胰岛素分泌和整体葡萄糖稳态。最近，人们对膳食生物活性物质增加循环 GLP-1 水平、从而增加胰岛素分泌和葡萄糖代谢的能力产生了浓厚的兴趣。
目的
我们评估了（-）-表儿茶素（EC）和不同花色苷（AC）及其代谢物对小鼠 GLP-1 代谢和 GLUTag 细胞的影响。
方法
我们用对照饮食或对照饮食加 40mgAC/kg 体重或 20mgEC/kg 体重喂养 6 周龄 C57BL/6J 雄性小鼠 14 周（AC）或 15 周（EC）。测量肠道 Gcg 和 Dpp-iv 的 mRNA 水平。在体外，用不同的 AC、其代谢物原儿茶酸（PCA）和 EC 孵育 GLUTag 细胞。评估 GLP-1 分泌及其释放的主要途径。
结果
长期补充 EC 或 AC 可增加小鼠 GLP-1 血浆浓度（分别增加 55%和 98%；P<0.05）。在小鼠中，1）EC 和 AC 分别增加空肠（91%）和结肠（41%）的 Gcg mRNA 水平（P<0.05）；2）AC 降低空肠 Dpp-iv mRNA 水平（35%），而 EC 降低血浆 DPP-IV 活性（15%；P<0.05）。在 GLUTag 细胞中，1）矢车菊素、天竺葵素、PCA 和 EC 均增加 GLP-1 分泌（分别增加 53%、33%、53%和 68%；P<0.05）；2）矢车菊素、天竺葵素、EC 和 PCA 增加环磷酸腺苷水平（25-50%；P<0.05）并激活蛋白激酶 A（PKA；分别增加 100%、50%、80%和 86%；P<0.05）。
结论
在小鼠中，EC 和 AC 调节 GLP-1 调节的不同步骤，导致血浆 GLP-1 增加。矢车菊素、天竺葵素、PCA 和 EC 通过激活 PKA 依赖性途径促进 GLUTag 细胞 GLP-1 的分泌。这些发现支持这些类黄酮通过调节 GLP-1 代谢在维持肠道和葡萄糖稳态方面的有益作用。
Zotero 插件