Transient receptor potential vanilloid 1 activation enhances gut glucagon-like peptide-1 secretion and improves glucose homeostasis.
Transient receptor potential vanilloid 1 activation enhances gut glucagon-like peptide-1 secretion and improves glucose homeostasis.
复制标题
瞬时受体电位 Vanilloid 1 激活增强肠道胰高血糖素样肽 1 分泌并改善血糖稳态
作者：
Wang P;Yan Z;Zhong J;Chen J;Ni Y;Li L;Ma L;Zhao Z;Liu D;Zhu Z
2 型糖尿病 (T2DM) 作为一个严重的全球健康问题正在迅速流行。目前 T2DM 的治疗可能会引起副作用，因此凸显了对更新、更安全疗法的需求。我们测试了这样的假设：膳食辣椒素通过激活肠道细胞和组织中瞬时受体电位香草酸 1 (TRPV1) 介导的胰高血糖素样肽 1 (GLP-1) 分泌来调节葡萄糖稳态。野生型 (WT) 和 TRPV1 敲除 (TRPV1−/−) 小鼠被喂食辣椒素 24 周。 TRPV1 定位于促胰液素肿瘤细胞 1 (STC-1) 细胞和回肠。辣椒素通过 TRPV1 激活以钙依赖性方式刺激 STC-1 细胞分泌 GLP-1。通过胃管饲法急性施用辣椒素会增加 WT 小鼠体内的 GLP-1 和胰岛素分泌，但在 TRPV1−/− 小鼠中则不会。此外，长期饮食辣椒素不仅可以改善 WT 小鼠的葡萄糖耐量和增加胰岛素水平，还可以降低每日血糖曲线并增加血浆 GLP-1 水平。然而，TRPV1−/− 小鼠中不存在这种效应。在 db/db 小鼠中，膳食辣椒素激活 TRPV1 可改善异常的葡萄糖稳态，并增加血浆和回肠中的 GLP-1 水平。目前的研究结果表明，TRPV1 激活刺激 GLP-1 分泌可能是干预糖尿病的一种有前途的方法。
Type 2 diabetes mellitus (T2DM) is rapidly prevailing as a serious global health problem. Current treatments for T2DM may cause side effects, thus highlighting the need for newer and safer therapies. We tested the hypothesis that dietary capsaicin regulates glucose homeostasis through the activation of transient receptor potential vanilloid 1 (TRPV1)-mediated glucagon-like peptide-1 (GLP-1) secretion in the intestinal cells and tissues. Wild-type (WT) and TRPV1 knockout (TRPV1−/−) mice were fed dietary capsaicin for 24 weeks. TRPV1 was localized in secretin tumor cell-1 (STC-1) cells and ileum. Capsaicin stimulated GLP-1 secretion from STC-1 cells in a calcium-dependent manner through TRPV1 activation. Acute capsaicin administration by gastric gavage increased GLP-1 and insulin secretion in vivo in WT but not in TRPV1−/− mice. Furthermore, chronic dietary capsaicin not only improved glucose tolerance and increased insulin levels but also lowered daily blood glucose profiles and increased plasma GLP-1 levels in WT mice. However, this effect was absent in TRPV1−/− mice. In db/db mice, TRPV1 activation by dietary capsaicin ameliorated abnormal glucose homeostasis and increased GLP-1 levels in the plasma and ileum. The present findings suggest that TRPV1 activation–stimulated GLP-1 secretion could be a promising approach for the intervention of diabetes.
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影响因子：
5
作者：
Gram, DX;Hansen, AJ;Ahrén, D
通讯作者：
Ahrén, D
DOI：
10.1016/j.bbrc.2004.06.149
发表时间：
2004-08-11
影响因子：
3.1
作者：
Akiba, Y;Kato, S;Hibi, T
通讯作者：
Hibi, T
影响因子：
6.9
作者：
Kang, Ji-Hye;Tsuyoshi, Goto;Yu, Rina
通讯作者：
Yu, Rina
影响因子：
3.4
作者：
Gram, Dorte X.;Ahren, Bo;Hansen, Anker J.
通讯作者：
Hansen, Anker J.
影响因子：
5.5
作者：
Ma, Shuangtao;Yu, Hao;Zhu, Zhiming
通讯作者：
Zhu, Zhiming