Phosphatidylinositol-3 kinase mediates the sweet suppressive effect of leptin in mouse taste cells.
Phosphatidylinositol-3 kinase mediates the sweet suppressive effect of leptin in mouse taste cells.
复制标题
DOI：
10.1111/jnc.15268
复制
发表时间：
2021-07
影响因子：
4.7
通讯作者：
Ninomiya Y
中科院分区：
文献类型：
--
作者：
Yoshida R;Margolskee RF;Ninomiya Y
已知瘦素可以选择性抑制神经和味觉细胞对甜味化合物的反应。瘦素的甜味抑制作用是由瘦素受体 Ob-Rb 和在一些对甜味敏感的味觉受体家族 1 成员 3 (T1R3) 阳性味觉细胞中表达的 ATP 门控 K+ (KATP) 通道介导的。然而，连接 Ob-Rb 和 KATP 通道的细胞内转导途径仍然未知。在这里，我们报道磷酸肌醇 3-激酶 (PI3K) 介导瘦素对 T1R3 阳性味觉细胞中甜味反应的抑制。在原位味觉细胞记录中，全身施用瘦素抑制了 T1R3 阳性味觉细胞中味觉细胞对蔗糖的反应。联合使用 PI3K 抑制剂（渥曼青霉素或 LY294002）会削弱瘦素对蔗糖反应的抑制作用。相比之下，虽然信号转导子和转录3激活剂以及包含Src同源区2结构域的磷酸酶2在T1R3阳性味觉细胞中表达，但同时给予信号转导子和转录3激活剂抑制剂(Stattic)或包含Src同源区2结构域的磷酸酶2抑制剂(SHP099)对瘦素对蔗糖反应的抑制没有影响。在去皮的舌上皮中，免疫组织化学在一些 T1R3 阳性味觉细胞中检测到磷脂酰肌醇 (3,4,5)-三磷酸的产生和瘦素对 AKT 的磷酸化，但在谷氨酸脱羧酶 67 阳性味觉细胞中未检测到。 LY294002 抑制瘦素诱导的磷脂酰肌醇 (3,4,5)-三磷酸的产生。因此，瘦素通过激活 Ob-Rb-PI3K-KATP 通道途径抑制 T1R3 阳性味觉细胞的甜味反应。
Leptin is known to selectively suppress neural and taste cell responses to sweet compounds. The sweet suppressive effect of leptin is mediated by the leptin receptor Ob-Rb, and the ATP-gated K+ (KATP) channel expressed in some sweet-sensitive, taste receptor family 1 member 3 (T1R3)-positive taste cells. However, the intracellular transduction pathway connecting Ob-Rb to KATP channel remains unknown. Here we report that phosphoinositide 3-kinase (PI3K) mediates leptin’s suppression of sweet responses in T1R3-positive taste cells. In in situ taste cell recording, systemically administrated leptin suppressed taste cell responses to sucrose in T1R3-positive taste cells. Such leptin’s suppression of sucrose responses was impaired by co-administration of PI3K inhibitors (wortmannin or LY294002). In contrast, co-administration of signal transducer and activator of transcription 3 inhibitor (Stattic) or Src homology region 2 domain-containing phosphatase-2 inhibitor (SHP099) had no effect on leptin’s suppression of sucrose responses, although signal transducer and activator of transcription 3 and Src homology region 2 domain-containing phosphatase-2 were expressed in T1R3-positive taste cells. In peeled tongue epithelium, phosphatidylinositol (3,4,5)-trisphosphate production and phosphorylation of AKT by leptin were immunohistochemically detected in some T1R3-positive taste cells but not in glutamate decarboxylase 67-positive taste cells. Leptin-induced phosphatidylinositol (3,4,5)-trisphosphate production was suppressed by LY294002. Thus, leptin suppresses sweet responses of T1R3-positive taste cells by activation of Ob-Rb–PI3K–KATP channel pathway.
登录
查看更多内容
对医疗统计信息的自由使用的易于使用的软件“ EZR”的调查。
影响因子：
4.8
作者：
Kanda Y
通讯作者：
Kanda Y
影响因子：
4.8
作者：
Gong, Yusong;Ishida-Takahashi, Ryoko;Myers, Martin G., Jr.
通讯作者：
Myers, Martin G., Jr.
影响因子：
7.7
作者：
Kieffer, TJ;Keller, RS;Habener, JF
通讯作者：
Habener, JF
影响因子：
3.5
作者：
Glendinning, John I.;Elson, Amanda E. T.;Munger, Steven D.
通讯作者：
Munger, Steven D.
影响因子：
5.5
作者：
McTaggart, James S.;Clark, Rebecca H.;Ashcroft, Frances M.
通讯作者：
Ashcroft, Frances M.