Fluoxetine improves glucose metabolism and regulates hepatic and neural gene expression in diabetic mice

This study investigated the impact of fluoxetine on glucose metabolism and gene regulation in diabetic mice. A total of 20 male Balb/c mice were divided into four groups: control, fluoxetine-treated non-diabetic, untreated diabetic, and fluoxetine-treated diabetic. Fluoxetine was given orally at a dosage of 25 mg/kg/day for 15 days.

The expression of several genes related to glucose metabolism, insulin, and neuroregulation was measured using real-time PCR. Fluoxetine treatment resulted in lower fasting blood glucose levels in diabetic mice, but did not affect AKT1 expression. Hepatic expression of GLUT4 and INSR was increased in fluoxetine-treated diabetic mice compared to untreated diabetics (p < 0.01).

In the brain, fluoxetine restored SIRT1 expression, reduced lncRNA NEAT1 levels, and increased lncRNA MEG3 levels in diabetic mice (p < 0.05, p < 0.01). Kidney tissue analysis revealed that fluoxetine partially reduced diabetic alterations, but did not fully restore renal histology. The results suggest that fluoxetine mainly affects glucose metabolism and neuroregulation, rather than providing structural protection.

While these findings offer preliminary evidence that fluoxetine might be a potential treatment for comorbid depression and diabetes, larger studies with more comprehensive metabolic analyses and protein-level validation are required to confirm these observations and understand the underlying mechanisms.