title: Fluoxetine-induced pancreatic beta cell dysfunction: New insight into the benefits of folic acid in the treatment of depression.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Here we examine the effects of the SSRI fluoxetine (Prozac®) on beta cell function utilizing INS-1E cells, a rat beta cell line, to elucidate the underlying molecular mechanisms.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These studies were conducted in vitro; the in vivo relevance remains to be determined.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, RM HSC-3N52 1280 Main Street West, Hamilton, ON, Canada L8S 4K1.
authors.forename: Nicole E
authors.initials: NE
authors.lastname: De Long
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, RM HSC-3N52 1280 Main Street West, Hamilton, ON, Canada L8S 4K1.
authors.forename: Jillian R
authors.initials: JR
authors.lastname: Hyslop
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, ON, Canada L8S 4K1.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Raha
authors.affiliation: Departments of Obstetrics and Gynecology and Physiology and Pharmacology, Western University, London, ON, Canada N6A5C1.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Hardy
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, RM HSC-3N52 1280 Main Street West, Hamilton, ON, Canada L8S 4K1. Electronic address: hollow@mcmaster.ca.
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
mesh_terms: D000818:Animals; D002460:Cell Line; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects* / Q000627:therapeutic use; D005492:Folic Acid / Q000627:therapeutic use; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D005473:Fluoxetine; D005492:Folic Acid; D017382:Reactive Oxygen Species; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Antidepressant; Beta cell; Folic acid; Mitochondrial dysfunction; Reactive oxygen species; Selective serotonin reuptake inhibitor