Selective Serotonin Reuptake Inhibitors (SSRIs) Inhibit Insulin Secretion and Action in Pancreatic β Cells*

Abstract

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 ␤ cells. Conclusion: SSRIs inhibit insulin signaling and beta cell function. Significance: SSRIs might accelerate the transition from an insulin-resistant state to overt diabetes.

Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes

“…Indeed, SSRIs (selective serotonin reuptake inhibitors) (e.g., paroxetine, fluoxetine, or sertraline) have been shown to inhibit both insulin secretion and insulin action in MIN-6 clonal beta cells [15]. Since SSRIs mainly act through inhibition of SERT, these effects are most likely attributed to an increase in 5-HT concentration in the extracellular space.…”

“…murine islet express both TPH1 and TPH2 [11,12], suggesting production of 5-HT. Previous studies have shown conflicting results of the effects of 5-HT on insulin secretion [8,13,14] and diabetogenic effects of atypical antipsychotics and antidepressants urges an increased understanding of peripheral effects of 5-HT modulating therapies upon glucose homeostasis [15].…”

Ion transfer stripping voltammetry for the detection of nanomolar levels of fluoxetine, citalopram, and sertraline in tap and river water samples

“…In cell 2, a Ag/AgCl reference electrode was used as the reference electrode in aqueous solution. The pH was maintained below the pKas of citalopram pKa (9.78), fluoxetine pKa (9.8), and sertraline hydrochloride pKa (9.85) [38][39][40], thus ensuring that the SSRIs were protonated and able to transfer through the PVC membrane to be detected as cations.…”

Energy Homeostasis by the Peripheral Serotonergic System

“…Furthermore, GSIS is obstructed by selective serotonin reuptake inhibitors (SSRIs) [18]. Shortterm treatment with SSRIs increases Ser/Thr phosphorylation of IRS-2 and inhibits IRS-2 functions and results in impaired GSIS from murine pancreatic islets.…”