Recent studies emphasize the importance of 5-HT2C receptor (5-HT_2CR) signaling in the regulation of energy homeostasis. The 5-HT_2CR is the only G-protein-coupled receptor known to undergo post-transcriptional adenosine to inosine (A-to-I) editing by adenosine deaminase acting on RNA (ADAR). 5-HT_2CR has emerged as an important role in the modulation of pancreatic β cell functions. This study investigated mechanisms behind the effects of palmitic acid (PA) on insulin secretion in different overexpressed 5-HT_2CR edited isoforms in pancreatic MIN6 β cells. Results showed that the expressions of 5HT_2CR and ADAR2 were upregulated in the pancreatic islets of mice fed with high-fat diet (HFD) compared to control mice. PA treatment significantly induced the expressions of 5-HT_2CR and ADAR2 in pancreatic MIN6 β cells. PA treatment significantly induced the editing of 5-HT_2CR in pancreatic MIN6 β cells. There was no significant difference in cell viability between naïve cells and three overexpressed 5-HT_2CR edited isoforms in pancreatic MIN6 β cells. Overexpressed 5-HT_2CR edited isoforms showed reduced glucose-stimulated insulin secretion (GSIS) compared with green fluorescent protein (GFP) expressed cells. Moreover, 5-HT_2CR edited isoforms displayed reduced endoplasmic reticulum (ER) calcium release and store-operated calcium entry (SOCE) activation, probably through inhibition of stromal interaction molecule 1 trafficking under PA treatment. Altogether, our results show that PA-mediated editing of 5-HT_2CR modulates GSIS through alteration of ER calcium release and SOCE activation in pancreatic MIN6 β cells.

中文翻译：

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5-HT2CR 的 RNA 编辑通过改变钙池操纵的钙进入损害胰腺 β 细胞的胰岛素分泌

最近的研究强调了 5-HT2C 受体 (5-HT _2C R) 信号在调节能量稳态中的重要性。5-HT _2C R 是唯一已知的 G 蛋白偶联受体，其通过作用于 RNA 的腺苷脱氨酶 (ADAR) 进行转录后腺苷到肌苷 (A-to-I) 编辑。5-HT _2C R 已在胰腺β 细胞功能的调节中发挥重要作用。本研究调查了棕榈酸 (PA) 对胰腺 MIN6 β 细胞中不同过表达 5-HT _2C R 编辑亚型中胰岛素分泌的影响背后的机制。结果表明，5HT _2C的表达与对照小鼠相比，高脂肪饮食 (HFD) 喂养的小鼠胰岛中的 R 和 ADAR2 上调。PA处理显着诱导胰腺MIN6β细胞中5-HT _2C R 和ADAR2的表达。PA 处理显着诱导胰腺 MIN6 β 细胞中 5-HT _2C R的编辑。原始细胞与胰腺 MIN6 β 细胞中三种过表达的 5-HT _2C R 编辑同种型之间的细胞活力没有显着差异。与绿色荧光蛋白 (GFP) 表达的细胞相比，过表达的 5-HT _2C R 编辑同种型显示葡萄糖刺激的胰岛素分泌 (GSIS) 减少。此外，5-HT _2CR 编辑的同种型显示出减少的内质网 (ER) 钙释放和钙池操纵的钙进入 (SOCE) 激活，这可能是通过抑制 PA 处理下的基质相互作用分子 1 运输。总之，我们的结果表明 PA 介导的 5-HT _2C R编辑通过改变胰腺 MIN6 β 细胞中的 ER 钙释放和 SOCE 激活来调节 GSIS。