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The selective serotonin reuptake inhibitor fluoxetine has direct effects on beta cells, promoting insulin secretion and increasing beta-cell mass

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)2038-2050
Number of pages13
JournalDiabetes, Obesity and Metabolism
Issue number10
Accepted/In press2022
PublishedOct 2022

Bibliographical note

Publisher Copyright: © 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

King's Authors


Aim: This study investigated whether therapeutically relevant concentrations of fluoxetine, which have been shown to reduce plasma glucose and glycated haemoglobin independent of changes in food intake and body weight, regulate beta-cell function and improve glucose homeostasis. Methods: Cell viability, insulin secretion, beta-cell proliferation and apoptosis were assessed after exposure of MIN6 beta cells or isolated mouse and human islets to 0.1, 1 or 10 μmol/L fluoxetine. The effect of fluoxetine (10 mg/kg body weight) administration on glucose homeostasis and islet function was also examined in ob/ob mice. Results: Exposure of MIN6 cells and mouse islets to 0.1 and 1 μmol/L fluoxetine for 72 hours did not compromise cell viability but 10 μmol/L fluoxetine significantly increased Trypan blue uptake. The dose of 1 μmol/L fluoxetine significantly increased beta-cell proliferation and protected islet cells from cytokine-induced apoptosis. In addition, 1 μmol/L fluoxetine induced rapid and reversible potentiation of glucose-stimulated insulin secretion from islets isolated from mice, and from lean and obese human donors. Finally, intraperitoneal administration of fluoxetine to ob/ob mice over 14 days improved glucose tolerance and resulted in significant increases in beta-cell proliferation and enhanced insulin secretory capacity. Conclusions: These data are consistent with a role for fluoxetine in regulating glucose homeostasis through direct effects on beta cells. Fluoxetine thus demonstrates promise as a preferential antidepressant for patients with concomitant occurrence of depression and diabetes.

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