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• W2000232109 endingPage "5693" @default.
• W2000232109 startingPage "5682" @default.
• W2000232109 abstract "Selective serotonin reuptake inhibitors (SSRIs) are antidepressants used for the treatment of mood and anxiety disorders. Here, we demonstrate that incubation (2 h) of murine islets or Min6 β cell line with the SSRIs paroxetine, fluoxetine, or sertraline inhibited insulin-induced Tyr phosphorylation of insulin receptor substrate (IRS)-2 protein and the activation of its downstream targets Akt and the ribosomal protein S6 kinase-1 (S6K1). Inhibition was dose-dependent with half-maximal effects at ∼15–20 μm. It correlated with a rapid dephosphorylation and activation of the IRS kinase GSK3β. Introduction of GSK3β siRNAs eliminated the inhibitory effects of the SSRIs. Inhibition of IRS-2 action by 30 μm SSRI was associated with a marked inhibition of glucose-stimulated insulin secretion from murine and human pancreatic islets. Secretion induced by basic secretagogues (KCl and Arg) was not affected by these drugs. Prolonged treatment (16 h) of Min6 cells with sertraline resulted in the induction of inducible nitric oxide synthase; activation of endoplasmic reticulum stress, and the initiation of the unfolded protein response, manifested by enhanced transcription of ATF4 and C/EBP homologous protein. This triggered an apoptotic process, manifested by enhanced caspase 3/7 activity, which resulted in β cell death. These findings implicate SSRIs as inhibitors of IRS protein function and insulin action through the activation of GSK3β. They further suggest that SSRIs inhibit insulin secretion; induce the unfolded protein response; activate an apoptotic process, and trigger β cell death. Given that SSRIs promote insulin resistance while inhibiting insulin secretion, these drugs might accelerate the transition from an insulin-resistant state to overt diabetes.Background: Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of mood and anxiety disorders.Results: SSRIs inhibit insulin action and secretion, promote the unfolded protein response, and induce apoptosis of pancreatic β cells.Conclusion: SSRIs inhibit insulin signaling and beta cell function.Significance: SSRIs might accelerate the transition from an insulin-resistant state to overt diabetes. Selective serotonin reuptake inhibitors (SSRIs) are antidepressants used for the treatment of mood and anxiety disorders. Here, we demonstrate that incubation (2 h) of murine islets or Min6 β cell line with the SSRIs paroxetine, fluoxetine, or sertraline inhibited insulin-induced Tyr phosphorylation of insulin receptor substrate (IRS)-2 protein and the activation of its downstream targets Akt and the ribosomal protein S6 kinase-1 (S6K1). Inhibition was dose-dependent with half-maximal effects at ∼15–20 μm. It correlated with a rapid dephosphorylation and activation of the IRS kinase GSK3β. Introduction of GSK3β siRNAs eliminated the inhibitory effects of the SSRIs. Inhibition of IRS-2 action by 30 μm SSRI was associated with a marked inhibition of glucose-stimulated insulin secretion from murine and human pancreatic islets. Secretion induced by basic secretagogues (KCl and Arg) was not affected by these drugs. Prolonged treatment (16 h) of Min6 cells with sertraline resulted in the induction of inducible nitric oxide synthase; activation of endoplasmic reticulum stress, and the initiation of the unfolded protein response, manifested by enhanced transcription of ATF4 and C/EBP homologous protein. This triggered an apoptotic process, manifested by enhanced caspase 3/7 activity, which resulted in β cell death. These findings implicate SSRIs as inhibitors of IRS protein function and insulin action through the activation of GSK3β. They further suggest that SSRIs inhibit insulin secretion; induce the unfolded protein response; activate an apoptotic process, and trigger β cell death. Given that SSRIs promote insulin resistance while inhibiting insulin secretion, these drugs might accelerate the transition from an insulin-resistant state to overt diabetes. Background: Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of mood and anxiety disorders. Results: SSRIs inhibit insulin action and secretion, promote the unfolded protein response, and induce apoptosis of pancreatic β cells. Conclusion: SSRIs inhibit insulin signaling and beta cell function. Significance: SSRIs might accelerate the transition from an insulin-resistant state to overt diabetes. Selective serotonin reuptake inhibitors (SSRIs) inhibit insulin secretion and action in pancreatic β cells.Journal of Biological ChemistryVol. 293Issue 12PreviewVOLUME 288 (2013) PAGES 5682–5693 Full-Text PDF Open Access" @default.
• W2000232109 created "2016-06-24" @default.
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• W2000232109 date "2013-02-01" @default.
• W2000232109 modified "2023-10-18" @default.
• W2000232109 title "Selective Serotonin Reuptake Inhibitors (SSRIs) Inhibit Insulin Secretion and Action in Pancreatic β Cells*" @default.
• W2000232109 cites W1515110997 @default.
• W2000232109 cites W1556383867 @default.
• W2000232109 cites W1697523131 @default.
• W2000232109 cites W1975988232 @default.
• W2000232109 cites W1977603207 @default.
• W2000232109 cites W1978492748 @default.
• W2000232109 cites W1987522063 @default.
• W2000232109 cites W1991334358 @default.
• W2000232109 cites W1992318224 @default.
• W2000232109 cites W1997146974 @default.
• W2000232109 cites W2001534460 @default.
• W2000232109 cites W2001649002 @default.
• W2000232109 cites W2003659422 @default.
• W2000232109 cites W2005233160 @default.
• W2000232109 cites W2005399725 @default.
• W2000232109 cites W2007179066 @default.
• W2000232109 cites W2017484264 @default.
• W2000232109 cites W2023140156 @default.
• W2000232109 cites W2023662309 @default.
• W2000232109 cites W2024921750 @default.
• W2000232109 cites W2026145411 @default.
• W2000232109 cites W2027727753 @default.
• W2000232109 cites W2033256254 @default.
• W2000232109 cites W2041767121 @default.
• W2000232109 cites W2043106623 @default.
• W2000232109 cites W2045359670 @default.
• W2000232109 cites W2048294768 @default.
• W2000232109 cites W2049117288 @default.
• W2000232109 cites W2049875806 @default.
• W2000232109 cites W2050486415 @default.
• W2000232109 cites W2057657052 @default.
• W2000232109 cites W2063351843 @default.
• W2000232109 cites W2064787111 @default.
• W2000232109 cites W2065789432 @default.
• W2000232109 cites W2067096633 @default.
• W2000232109 cites W2071070948 @default.
• W2000232109 cites W2071214152 @default.
• W2000232109 cites W2072303208 @default.
• W2000232109 cites W2079507344 @default.
• W2000232109 cites W2081359005 @default.
• W2000232109 cites W2089198803 @default.
• W2000232109 cites W2090101620 @default.
• W2000232109 cites W2092162739 @default.
• W2000232109 cites W2101585433 @default.
• W2000232109 cites W2102909249 @default.
• W2000232109 cites W2102958377 @default.
• W2000232109 cites W2115251905 @default.
• W2000232109 cites W2115427222 @default.
• W2000232109 cites W2118787348 @default.
• W2000232109 cites W2124360636 @default.
• W2000232109 cites W2127151873 @default.
• W2000232109 cites W2135766812 @default.
• W2000232109 cites W2139191784 @default.
• W2000232109 cites W2141063928 @default.
• W2000232109 cites W2145869245 @default.
• W2000232109 cites W2146921827 @default.
• W2000232109 cites W2147825853 @default.
• W2000232109 cites W2163725144 @default.
• W2000232109 cites W2170534338 @default.
• W2000232109 cites W2171799186 @default.
• W2000232109 cites W2465651915 @default.
• W2000232109 cites W4214707413 @default.
• W2000232109 cites W4240809199 @default.
• W2000232109 doi "https://doi.org/10.1074/jbc.m112.408641" @default.
• W2000232109 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5868260" @default.
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