Selective serotonin reuptake inhibitors (SSRIs) inhibit insulin secretion and action in pancreatic β cells.

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

SUBMITTER: Isaac R 

PROVIDER: S-EPMC3581374 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature