Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.
Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.
复制标题
DOI：
10.1371/journal.pone.0005106
复制
发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Kojima I
中科院分区：
文献类型：
--
作者：
Nakagawa Y;Nagasawa M;Yamada S;Hara A;Mogami H;Nikolaev VO;Lohse MJ;Shigemura N;Ninomiya Y;Kojima I
甜味受体在味蕾和肠内分泌细胞中表达，作为糖的感知器。我们研究了甜味受体在MIN6细胞和小鼠胰岛中的表达和功能。采用RT-PCR和免疫组织化学检测甜味受体的表达。使用fura-2和epac1 - cAMP监测MIN6细胞胞质Ca2+ ([Ca2+]c)和cAMP （[cAMP]c）的变化。通过测定marks - gfp的易位来监测蛋白激酶C的活化。用放射免疫法测定胰岛素。在MIN6细胞中表达T1R2、T1R3和gustducin的mRNA。在这些细胞中，人工甜味剂如三氯蔗糖、糖精和乙酰氨基磺酸- k增加了胰岛素分泌，并增强了葡萄糖诱导的分泌。三氯蔗糖增加了[Ca2+]c的双相增加。第二个持续期通过去除细胞外钙和加入硝苯地平来阻断。肌醇(1,4,5)-三磷酸腺苷受体抑制剂2-氨基乙氧基二苯硼酸盐阻断了[Ca2+]c反应的两个阶段。三氯蔗糖对[Ca2+]c的影响被甘豆素（一种甜味受体抑制剂）抑制，但不受Gq抑制剂的影响。三氯蔗糖还能诱导[cAMP]c持续升高，但通过去除细胞外钙和硝苯地平只能部分抑制。最后，小鼠胰岛表达T1R2和T1R3，人工甜味剂刺激胰岛素分泌。甜味受体在β-细胞中表达，该受体的激活通过Ca2+和camp依赖机制诱导胰岛素分泌。
Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets. The expression of the sweet taste receptor was determined by RT–PCR and immunohistochemistry. Changes in cytoplasmic Ca2+ ([Ca2+]c) and cAMP ([cAMP]c) were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was monitored by measuring translocation of MARCKS-GFP. Insulin was measured by radioimmunoassay. mRNA for T1R2, T1R3, and gustducin was expressed in MIN6 cells. In these cells, artificial sweeteners such as sucralose, succharin, and acesulfame-K increased insulin secretion and augmented secretion induced by glucose. Sucralose increased biphasic increase in [Ca2+]c. The second sustained phase was blocked by removal of extracellular calcium and addition of nifedipine. An inhibitor of inositol(1, 4, 5)-trisphophate receptor, 2-aminoethoxydiphenyl borate, blocked both phases of [Ca2+]c response. The effect of sucralose on [Ca2+]c was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a Gq inhibitor. Sucralose also induced sustained elevation of [cAMP]c, which was only partially inhibited by removal of extracellular calcium and nifedipine. Finally, mouse islets expressed T1R2 and T1R3, and artificial sweeteners stimulated insulin secretion. Sweet taste receptor is expressed in β-cells, and activation of this receptor induces insulin secretion by Ca2+ and cAMP-dependent mechanisms.
登录
查看更多内容
影响因子：
2.5
作者：
Hara, Akemi;Kadoya, Yuichi;Yamashina, Shohei
通讯作者：
Yamashina, Shohei
影响因子：
9.2
作者：
Nie, Y;Vigues, S;Munger, SD
通讯作者：
Munger, SD
影响因子：
7.7
作者：
Matschinsky, FM
通讯作者：
Matschinsky, FM
影响因子：
29
作者：
Reimann F;Habib AM;Tolhurst G;Parker HE;Rogers GJ;Gribble FM
通讯作者：
Gribble FM
影响因子：
4
作者：
Cheng, Henrique;Beck, Andreas;Penner, Reinhold
通讯作者：
Penner, Reinhold