RNA editing of 5-HT2CR impairs insulin secretion of pancreatic beta cells via altered store-operated calcium entry

Ke Yun Xie, Shao Ju Chien, Bertrand Chin Ming Tan, Yun Wen Chen

研究成果: Article同行評審

摘要

Recent studies emphasize the importance of 5-HT2C receptor (5-HT2CR) signaling in the regulation of energy homeostasis. The 5-HT2CR 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-HT2CR 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-HT2CR edited isoforms in pancreatic MIN6 β cells. Results showed that the expressions of 5HT2CR 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-HT2CR and ADAR2 in pancreatic MIN6 β cells. PA treatment significantly induced the editing of 5-HT2CR in pancreatic MIN6 β cells. There was no significant difference in cell viability between naïve cells and three overexpressed 5-HT2CR edited isoforms in pancreatic MIN6 β cells. Overexpressed 5-HT2CR edited isoforms showed reduced glucose-stimulated insulin secretion (GSIS) compared with green fluorescent protein (GFP) expressed cells. Moreover, 5-HT2CR 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-HT2CR modulates GSIS through alteration of ER calcium release and SOCE activation in pancreatic MIN6 β cells.

原文English
文章編號e21929
期刊FASEB Journal
35
發行號10
DOIs
出版狀態Published - 2021 十月

All Science Journal Classification (ASJC) codes

  • 生物技術
  • 生物化學
  • 分子生物學
  • 遺傳學

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