Fluoxetine-induced pancreatic beta cell dysfunction: New insight into the benefits of folic acid in the treatment of depression
| Autor: | Daniel B. Hardy, Alison C. Holloway, Nicole E. De Long, Jillian R. Hyslop, Sandeep Raha |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Type 2 diabetes medicine.disease_cause Cell Line 03 medical and health sciences 0302 clinical medicine Folic Acid Internal medicine Diabetes mellitus Fluoxetine Insulin-Secreting Cells medicine Animals Humans Depression (differential diagnoses) 030304 developmental biology 0303 health sciences Depressive Disorder Major business.industry medicine.disease 3. Good health Rats Psychiatry and Mental health Clinical Psychology Endocrinology Major depressive disorder Antidepressant Female Beta cell business Reactive Oxygen Species 030217 neurology & neurosurgery Oxidative stress Selective Serotonin Reuptake Inhibitors medicine.drug |
| Zdroj: | Journal of affective disorders. 166 |
| ISSN: | 1573-2517 |
| Popis: | 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. Limitations 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. |
| Databáze: | OpenAIRE |
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