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J Affect Disord. 2014 Sep;166:6-13. doi: 10.1016/j.jad.2014.04.063. Epub 2014 May 4.

Fluoxetine-induced pancreatic beta cell dysfunction: New insight into the benefits of folic acid in the treatment of depression.

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Department of Obstetrics and Gynecology, McMaster University, RM HSC-3N52 1280 Main Street West, Hamilton, ON, Canada L8S 4K1.
Department of Pediatrics, McMaster University, Hamilton, ON, Canada L8S 4K1.
Departments of Obstetrics and Gynecology and Physiology and Pharmacology, Western University, London, ON, Canada N6A5C1.
Department of Obstetrics and Gynecology, McMaster University, RM HSC-3N52 1280 Main Street West, Hamilton, ON, Canada L8S 4K1. Electronic address:



Major depressive disorder is a common psychiatric illness with reported prevalence rates of 12-16% in persons aged 12 and over. Depression is also associated with a high risk of new onset of type 2 diabetes (T2D). This relationship between depression and diabetes may be related to depression itself and/or drugs prescribed. Importantly, the use of selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed class of antidepressants, increases the risk of developing T2D. However, the mechanism(s) underlying this association remains elusive.


Here we examine the effects of the SSRI fluoxetine (ProzacĀ®) on beta cell function utilizing INS-1E cells, a rat beta cell line, to elucidate the underlying molecular mechanisms.


Fluoxetine treatment significantly reduced glucose stimulated insulin secretion (GSIS). This decreased beta cell function was concomitant with an increased production of reactive oxygen species and oxidative damage which may contribute to decreased mitochondrial electron transport chain enzyme (ETC) activity. Importantly the fluoxetine-induced deficits in beta cell function were prevented by the addition of the antioxidant folic acid.


These studies were conducted in vitro; the in vivo relevance remains to be determined.


These findings suggest that use of SSRI antidepressants may increase the risk of new-onset T2D by causing oxidative stress in pancreatic beta cells. However, folic acid supplementation in patients taking SSRIs may reduce the risk of new onset diabetes via protection of normal beta cell function.


Antidepressant; Beta cell; Folic acid; Mitochondrial dysfunction; Reactive oxygen species; Selective serotonin reuptake inhibitor

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