Characterization of taste receptor-related G-protein α-gustducin in pancreatic β-cells.
Characterization of taste receptor-related G-protein α-gustducin in pancreatic β-cells.
复制标题
胰腺 β 细胞中味觉受体相关 G 蛋白 α-gustducin 的表征。
DOI：
10.1111/jdi.13214
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Yasuda K.
中科院分区：
文献类型：
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作者：
Udagawa H;Hiramoto M;Kawaguchi M;Uebanso T;Ohara-Imaizumi M;Nammo T;Nishimura W;Yasuda K.
味觉受体（T1rs和T2rs）和味觉选择性G蛋白（α - gustducin）在味觉感知系统外表达，如肠内分泌L细胞。在这里，我们研究了α - gustducin是否也影响胰腺β细胞的营养感知和胰岛素分泌。材料与方法采用定量聚合酶链反应或荧光免疫染色法检测β -细胞系、大鼠和小鼠胰岛中α -味觉素和味觉受体的表达。α - gustducin敲低对大鼠INS - 1细胞胰岛素分泌、单磷酸环腺苷和细胞内Ca2+水平的影响。在α - gustducin抑制的INS - 1细胞和小鼠疾病模型的胰岛中，研究了三氯蔗糖（味觉受体激动剂）诱导的胰岛素分泌。结果Tas1r3和α - gustducin在β -细胞系和胰岛中均有表达。α - gustducin的下调显著提高了INS - 1细胞中环磷酸腺苷、细胞内钙和胰岛素分泌的基础水平。α - gustducin在高脂饮食小鼠和糖尿病小鼠中表达降低。在敲低α - gustducin的INS - 1细胞或α - gustducin表达降低的小鼠胰岛中，三氯蔗糖诱导的胰岛素分泌并未减弱。结论α - Gustducin以独立于味觉受体信号传导的方式参与胰腺β -细胞中环腺苷单磷酸、细胞内钙水平和胰岛素分泌的调节。α - Gustducin可能在β -细胞生理和2型糖尿病的发展中发挥新的作用。
Aims/IntroductionTaste receptors, T1rs and T2rs, and the taste‐selective G‐protein, α‐gustducin, are expressed outside the taste‐sensing system, such as enteroendocrine L cells. Here, we examined whether α‐gustducin also affects nutrition sensing and insulin secretion by pancreatic β‐cells.Materials and MethodsThe expression of α‐gustducin and taste receptors was evaluated in β‐cell lines, and in rat and mouse islets either by quantitative polymerase chain reaction or fluorescence immunostaining. The effects of α‐gustducin knockdown on insulin secretion and on cyclic adenosine monophosphate and intracellular Ca2+levels in rat INS‐1 cells were estimated. Sucralose (taste receptor agonist)‐induced insulin secretion was investigated in INS‐1 cells with α‐gustducin suppression and in islets from mouse disease models.ResultsThe expression of Tas1r3 and α‐gustducin was confirmed in β‐cell lines and pancreatic islets. Basal levels of cyclic adenosine monophosphate, intracellular calcium and insulin secretion were significantly enhanced with α‐gustducin knockdown in INS‐1 cells.The expression of α‐gustducin was decreased in high‐fat diet‐fed mice and in diabeticdb/dbmice. Sucralose‐induced insulin secretion was not attenuated in INS‐1 cells with α‐gustducin knockdown or in mouse islets with decreased expression of α‐gustducin.Conclusionsα‐Gustducin is involved in the regulation of cyclic adenosine monophosphate, intracellular calcium levels and insulin secretion in pancreatic β‐cells in a manner independent of taste receptor signaling. α‐Gustducin might play a novel role in β‐cell physiology and the development of type 2 diabetes.