The Anthocyanin Delphinidin 3-Rutinoside Stimulates Glucagon-Like Peptide-1 Secretion in Murine GLUTag Cell Line via the Ca2+/Calmodulin-Dependent Kinase II Pathway.
The Anthocyanin Delphinidin 3-Rutinoside Stimulates Glucagon-Like Peptide-1 Secretion in Murine GLUTag Cell Line via the Ca2+/Calmodulin-Dependent Kinase II Pathway.
复制标题
花色苷Delphinidin 3-鲁丁苷刺激通过Ca2+/钙调蛋白依赖性激酶II途径刺激鼠谷物细胞系中胰高血糖素样肽-1分泌。
DOI：
10.1371/journal.pone.0126157
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tsuda T
中科院分区：
文献类型：
--
作者：
Kato M;Tani T;Terahara N;Tsuda T
胰高血糖素样肽-1（GLP-1）是由肠内分泌L细胞分泌的肠促胰岛素激素。虽然几种营养素诱导GLP-1分泌，但几乎没有证据表明非营养化合物直接增加GLP-1分泌。在这里，我们假设花青素诱导GLP-1分泌，从而显著有助于预防和治疗糖尿病。飞燕草素3-芸香糖苷（D3 R）显示增加GLUTag L细胞中的GLP-1分泌。结果表明，芳香环上的三个羟基或两个甲氧基部分对于刺激GLP-1分泌是必需的。值得注意的是，芸香糖部分显示为GLP-1分泌的有效增强剂，但仅与芳环上的三个羟基部分（D3 R）结合。受体拮抗剂研究表明，D3 R刺激GLP-1分泌，涉及肌醇1，4，5-三磷酸受体介导的细胞内Ca 2+动员。用Ca 2 +/钙调蛋白依赖性激酶II（CaMKII）抑制剂（KN-93）处理GLUTag细胞可消除D3 R刺激的GLP-1分泌。此外，用D3 R处理GLUTag细胞导致CaMKII活化。用G蛋白偶联受体（GPR）40/120拮抗剂（GW 1100）预处理细胞也显著降低了D3 R刺激的GLP-1分泌。这些观察结果表明，D3 R刺激GLUTag细胞中的GLP-1分泌，D3 R刺激GLP-1分泌是通过Ca 2 +-CaMKII途径介导的，这可能是由GPR 40/120介导的。这些发现提供了食物或药物介导的肠道L细胞中GLP-1分泌的可能分子机制，并证明了花青素在GLP-1分泌方面的新生物学功能。
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from enteroendocrine L-cells. Although several nutrients induce GLP-1 secretion, there is little evidence to suggest that non-nutritive compounds directly increase GLP-1 secretion. Here, we hypothesized that anthocyanins induce GLP-1 secretion and thereby significantly contribute to the prevention and treatment of diabetes. Delphinidin 3-rutinoside (D3R) was shown to increase GLP-1 secretion in GLUTag L cells. The results suggested that three hydroxyl or two methoxyl moieties on the aromatic ring are essential for the stimulation of GLP-1 secretion. Notably, the rutinose moiety was shown to be a potent enhancer of GLP-1 secretion, but only in conjunction with three hydroxyl moieties on the aromatic ring (D3R). Receptor antagonist studies revealed that D3R-stimulates GLP-1 secretion involving inositol 1,4,5-trisphosphate receptor-mediated intracellular Ca2+ mobilization. Treatment of GLUTag cells with a Ca2+/calmodulin-dependent kinaseII (CaMKII) inhibitor (KN-93) abolished D3R-stimulated GLP-1 secretion. In addition, treatment of GLUTag cells with D3R resulted in activation of CaMKII. Pre-treatment of cells with a G protein-coupled receptor (GPR) 40/120 antagonist (GW1100) also significantly decreased D3R-stimulated GLP-1 secretion. These observations suggest that D3R stimulates GLP-1 secretion in GLUTag cells, and that stimulation of GLP-1 secretion by D3R is mediated via Ca2+-CaMKII pathway, which may possibly be mediated by GPR40/120. These findings provide a possible molecular mechanism of GLP-1 secretion in intestinal L-cells mediated by foods or drugs and demonstrate a novel biological function of anthocyanins in regards to GLP-1 secretion.
登录
查看更多内容
影响因子：
4.8
作者：
Lim, Gareth E.;Xu, Molie;Brubaker, Patricia L.
通讯作者：
Brubaker, Patricia L.
影响因子：
4.8
作者：
Mahadev, K;Wu, XD;Goldstein, BJ
通讯作者：
Goldstein, BJ
影响因子：
3.8
作者：
Lee, Soo-Jin;Kim, Hyo-Eun;Kang, Yup
通讯作者：
Kang, Yup
影响因子：
7.7
作者：
Edfalk S;Steneberg P;Edlund H
通讯作者：
Edlund H
影响因子：
7.7
作者：
DEACON, CF;NAUCK, MA;HOLST, JJ
通讯作者：
HOLST, JJ