Selective serotonin reuptake inhibitor, fluoxetine, impairs E-cadherin-mediated cell adhesion and alters calcium homeostasis in pancreatic beta cells
| العنوان: | Selective serotonin reuptake inhibitor, fluoxetine, impairs E-cadherin-mediated cell adhesion and alters calcium homeostasis in pancreatic beta cells |
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| المؤلفون: | Meng Ru Shen, Yun Wen Chen, Mei Lang Kung, Shu Ling Chen, Lee-Ming Chuang, Huang Yu Chang |
| المصدر: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
| بيانات النشر: | Nature Publishing Group UK, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Science, Serotonin reuptake inhibitor, chemistry.chemical_element, Fluorescent Antibody Technique, Calcium, Biology, Endoplasmic Reticulum, Calcium in biology, Article, Cell Line, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, Cytochrome P-450 CYP2D6 Inhibitors, Fluoxetine, Insulin-Secreting Cells, medicine, Cell Adhesion, Animals, Homeostasis, Cell adhesion, Calcium metabolism, Multidisciplinary, Cadherin, STIM1, Cadherins, 030104 developmental biology, Endocrinology, chemistry, 030220 oncology & carcinogenesis, Medicine, Antidepressive Agents, Second-Generation, Selective Serotonin Reuptake Inhibitors, medicine.drug |
| الوصف: | Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for mood disorders. Long term use of SSRIs is associated with an increased risk of diabetes, but the underlying mechanism(s) remains elusive. E-cadherin-mediated cell-cell adhesion and elevated [Ca2+]i are important for insulin release and pancreatic β cell functions. This study aims to investigate whether a SSRI, fluoxetine (Prozac), induces pancreatic β cell dysfunction through affecting E-cadherin and/or [Ca2+]i. Here we show that fluoxetine significantly reduces glucose stimulated insulin secretion (GSIS). MIN6 cells, an established murine immortalized β cell line, form smaller colonies of loosely packed cells with reduced cell-cell contact after fluoxetine treatment. Immunofluorescence staining reveals that fluoxetine increases cytoplasmic accumulation of E-cadherin and reduces the membrane-localized E-cadherin probably due to increase of its endocytosis. Fluoxetine inhibits spreading of β cells on E-cad/Fc coated slides and also disrupts E-cadherin-mediated actin filaments. Additionally, fluoxetine significantly suppresses endoplasmic reticulum (ER) calcium release and store-operated calcium entry (SOCE) activation, probably through reduction of ER calcium storage and inhibition of stromal interaction molecule 1 (STIM1) trafficking. These data suggest that exposure to fluoxetine results in impaired β cell functions, occurring in concert with reduction of E-cadherin-dependent cell adhesion and alterations of calcium homeostasis. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f50a4246c4a995d93ba54f8e94fde9b3Test http://europepmc.org/articles/PMC5471211Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f50a4246c4a995d93ba54f8e94fde9b3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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