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

Isaac, Roi; Boura‐Halfon, Sigalit; Gurevitch, Diana; Shainskaya, Alla; Levkovitz, Yechiel; Zick, Yehiel

doi:10.1074/jbc.aac118.002476

Cited by 3 publications

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“…Following are the possible mechanisms of diabetes caused by SSRIs. Boura-Halfon et al have shown that SSRIs are potential inducers of insulin resistance, and its role may be to act as a direct inhibitor of the insulin signaling cascade in β-cells [ 33 ]. The mechanism of short-term inhibition of insulin by SSRIs may involve activating IRS-2 (insulin receptor substrate proteins-2) kinase, such as GSK 3 β, and promoting the phosphorylation of IRS-2 at some inhibitory Ser sites.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of short-term inhibition of insulin by SSRIs may involve activating IRS-2 (insulin receptor substrate proteins-2) kinase, such as GSK 3 β, and promoting the phosphorylation of IRS-2 at some inhibitory Ser sites. He also found that GSK 3 β was a key factor in inhibition, including inhibition of protein function of IRS-2 and inhibition of GSIS (glucose-stimulated insulin secretion) [ 33 ]. On the other hand, by biochemical analysis and electrophysiological analysis, Paulmann et al [ 34 ] found that 5-HT regulates insulin secretion by serotonylation of GTPases within pancreatic β-cells, and SSRIs can block this intracellular process, resulting in inhibition of insulin secretion in β-cells.…”

Section: Discussionmentioning

confidence: 99%

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The effect of selective serotonin re-uptake inhibitors on risk of type II diabetes mellitus and acute pancreatitis: a meta-analysis

Yao

Fan

et al. 2018

Bioscience Reports

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To explore the effect of selective serotonin re-uptake inhibitors (SSRIs) on risk of type II diabetes mellitus (T2DM) and acute pancreatitis (AP), expecting to provide guidance for clinic. Literature was retrieved by searching Pubmed, Embase, Cochrane and Scopus and hand searching of reference lists of related articles. Stata 14.0 was utilized for processing and analysis, and adjusted odds ratios (aORs) were applied. Our study included 113898 T2DM patients and 284131 controls from nine studies and 17548 AP patients and 108108 controls from four studies. The pooled aORs of SSRIs on the risk of T2DM and AP were 1.38 (95% confidence interval (CI) = 1.24–1.54) and 1.26 (95% CI = 1.13–1.40), respectively. Study design, quality, ethnicity, follow-up, and sample size of patients were the resources of heterogeneity. Subgroup analysis showed that 2 weeks is a high-risk time for AP after SSRIs use, with 1.48-fold-times as much after it. This meta-analysis provides evidence of a significant positive association between SSRIs use and risks of T2DM or AP, and duration of 2 weeks of SSRIs use has higher risk of AP, which should be paid much attention to.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The effect of selective serotonin re-uptake inhibitors on risk of type II diabetes mellitus and acute pancreatitis: a meta-analysis

Yao

Fan

et al. 2018

Bioscience Reports

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Antidepressant continuation in pregnancy and risk of gestational diabetes

Wartko

Weiss

Enquobahrie

et al. 2019

Pharmacoepidemiology and Drug

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Purpose Previous studies observed modestly higher risk of gestational diabetes (GDM) associated with antidepressant use in pregnancy, potentially due to confounding by indication. We assessed the association of antidepressant continuation in pregnancy with GDM, as well as blood glucose levels, after accounting for confounding. Methods We conducted a retrospective cohort study of singleton live births from 2001 to 2014 to women enrolled in Kaiser Permanente Washington, an integrated health care delivery system, utilizing electronic health data and linked Washington State birth records. We required that women have ≥1 antidepressant prescription fills ≤6 months before pregnancy. Women with an antidepressant fill during pregnancy were categorized as “continuers” (n = 1634); those without a fill were “discontinuers” (n = 1211). We calculated relative risks (RRs) for GDM and mean differences in screening blood glucose levels using generalized estimating equations with inverse probability of treatment weighting to account for baseline characteristics, including mental health conditions and indicators of mental health severity. Results Compared with discontinuers, antidepressant continuers had comparable risk of GDM (RR: 1.10; 95% confidence interval [CI], 0.84‐1.44) and blood glucose levels (mean difference: 2.3 mg/dL; 95% CI, −1.5 to 6.1 mg/dL). We observed generally similar results for specific antidepressants, with the potential exceptions of risk of GDM associated with sertraline (RR: 1.30; 95% CI, 0.90‐1.88) and venlafaxine (RR: 1.52; 95% CI, 0.87‐2.68), but neither association was statistically significant. Conclusions Our study suggests that overall, women who continue antidepressants in pregnancy are not at increased risk for GDM or higher blood glucose, although further study may be warranted for sertraline and venlafaxine.

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Antidepressant use during pregnancy and the risk of gestational diabetes mellitus: a nested case–control study

2019

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ObjectivesThe aim of this study was to determine the association between antidepressant (AD) classes, types and duration of use during pregnancy and the risk of gestational diabetes mellitus (GDM).Design and settingA nested case–control study was conducted within the Quebec Pregnancy Cohort (QPC), a Canadian provincial database which includes data on all pregnancies and children in Quebec from January 1998 to December 2015.Primary outcome measuresGestational diabetes mellitus.ParticipantsCases of GDM were identified after week 20 of pregnancy and randomly matched 1:10 to controls on gestational age at index date (ie, calendar date of GDM) and year of pregnancy. AD exposure was assessed by filled prescriptions between the beginning of pregnancy (first day of last menstrual period) and index date. Conditional logistic regression models were used to estimate crude and adjusted odds ratios (aOR).ResultsAmong 20 905 cases and 209 050 matched controls, 9741 (4.2%) women were exposed to ADs. When adjusting for potential confounders, AD use was associated with an increased risk of GDM (aOR 1.19, 95% CI 1.08 to 1.30); venlafaxine (aOR 1.27, 95% CI 1.09 to 1.49) and amitriptyline (aOR 1.52, 95% CI 1.25 to 1.84) were also associated with an increased risk of GDM. Moreover, the risk of GDM was increased with longer duration of AD use, specifically for serotonin norepinephrine reuptake inhibitors, tricyclic ADs and combined use of two AD classes. No statistically significant association was observed for selective serotonin reuptake inhibitors.ConclusionThe findings suggest that ADs—and specifically venlafaxine and amitriptyline—were associated with an increased risk of GDM.

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

Abstract: Figs. 1B, 2A, 3A, 4B, 5A, and 7 did not indicate the borders between the images. This error has now been corrected and does not affect the results or conclusions of this work.

Cited by 3 publications

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The effect of selective serotonin re-uptake inhibitors on risk of type II diabetes mellitus and acute pancreatitis: a meta-analysis

The effect of selective serotonin re-uptake inhibitors on risk of type II diabetes mellitus and acute pancreatitis: a meta-analysis

Antidepressant continuation in pregnancy and risk of gestational diabetes

Antidepressant use during pregnancy and the risk of gestational diabetes mellitus: a nested case–control study

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