Selective serotonin reuptake inhibitor, fluoxetine, impairs E-cadherin-mediated cell adhesion and alters calcium homeostasis in pancreatic beta cells

Huang Yu Chang, Shu Ling Chen, Meng Ru Shen, Mei Lang Kung, Lee Ming Chuang, Yun Wen Chen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 [Ca 2+ ] 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 [Ca 2+ ]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.

Original languageEnglish
Article number3515
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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Fluoxetine
Serotonin Uptake Inhibitors
Insulin-Secreting Cells
Cadherins
Cell Adhesion
Homeostasis
Calcium
Endoplasmic Reticulum
Insulin
Endocytosis
Mood Disorders
Actin Cytoskeleton
Fluorescent Antibody Technique
Staining and Labeling
Glucose
Cell Line
Membranes

All Science Journal Classification (ASJC) codes

  • General

Cite this

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title = "Selective serotonin reuptake inhibitor, fluoxetine, impairs E-cadherin-mediated cell adhesion and alters calcium homeostasis in pancreatic beta cells",
abstract = "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 [Ca 2+ ] 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 [Ca 2+ ]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.",
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Selective serotonin reuptake inhibitor, fluoxetine, impairs E-cadherin-mediated cell adhesion and alters calcium homeostasis in pancreatic beta cells. / Chang, Huang Yu; Chen, Shu Ling; Shen, Meng Ru; Kung, Mei Lang; Chuang, Lee Ming; Chen, Yun Wen.

In: Scientific reports, Vol. 7, No. 1, 3515, 01.12.2017.

Research output: Contribution to journalArticle

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AU - Chang, Huang Yu

AU - Chen, Shu Ling

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AU - Kung, Mei Lang

AU - Chuang, Lee Ming

AU - Chen, Yun Wen

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