Fluoxetine regulates glucose and lipid metabolism via the PI3KAKT signaling pathway in diabetic rats.
Mol Med Rep
; 22(4): 3073-3080, 2020 Oct.
Article
em En
| MEDLINE
| ID: mdl-32945450
ABSTRACT
Diabetes mellitus poses a major threat towards global heath due to a lack of effective treatment. Fluoxetine hydrochloride, a selective 5hydroxytryptamine reuptake inhibitor, is the most commonly used antidepressant in clinical therapy; however, the potential molecular mechanisms of fluoxetine in diabetes remain unknown. In the present study, reduced glucose, total cholesterol and triglyceride levels and lipid metabolism, as well as upregulated proliferatoractivated receptor γ, fatty acid synthase and lipoprotein lipase, and downregulated sterol regulatory elementbinding protein 1c were detected in rats with streptozotocin (STZ)induced diabetes following treatment with fluoxetine. Furthermore, fluoxetine significantly inhibited the expression levels of glucose metabolismassociated proteins in liver tissues, including glycogen synthase kinase 3ß (GSK3ß), glucose6 phosphatase catalytic subunit (G6PC), phosphoenolpyruvate carboxykinase (PEPCK) and forkhead box protein O1 (FOXO1). In addition, fluoxetine treatment notably attenuated morphological liver damage in rats with STZinduced diabetes. Additionally, fluoxetine could inhibit the phosphatidylinositol 3kinaseprotein kinase B (PI3KAKT) signaling pathway, whereas LY294002, a specific inhibitor of PI3K, suppressed the function of PI3KAKT signaling and suppressed the expression levels of glucose metabolismassociated proteins, including GSK3ß, G6PC, PEPCK and FOXO1 in BRL3A cells. The results of the present study revealed that fluoxetine may regulate glucose and lipid metabolism via the PI3KAKT signaling pathway in diabetic rats.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Fluoxetina
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Diabetes Mellitus Experimental
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Diabetes Mellitus Tipo 2
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Metabolismo dos Lipídeos
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2020
Tipo de documento:
Article