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Fluoxetine regulates glucose and lipid metabolism via the PI3K-AKT signaling pathway in diabetic rats

Diabetes mellitus poses a major threat towards global heath due to a lack of effective treatment. Fluoxetine hydrochloride, a selective 5-hydroxytryptamine reuptake inhibitor, is the most commonly used antidepressant in clinical therapy; however, the potential molecular mechanisms of fluoxetine in d...

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Autores principales: Yang, Hailong, Cao, Qiuyun, Xiong, Xiaolu, Zhao, Peng, Shen, Diwen, Zhang, Yuzhe, Zhang, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453494/
https://www.ncbi.nlm.nih.gov/pubmed/32945450
http://dx.doi.org/10.3892/mmr.2020.11416
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author Yang, Hailong
Cao, Qiuyun
Xiong, Xiaolu
Zhao, Peng
Shen, Diwen
Zhang, Yuzhe
Zhang, Ning
author_facet Yang, Hailong
Cao, Qiuyun
Xiong, Xiaolu
Zhao, Peng
Shen, Diwen
Zhang, Yuzhe
Zhang, Ning
author_sort Yang, Hailong
collection PubMed
description Diabetes mellitus poses a major threat towards global heath due to a lack of effective treatment. Fluoxetine hydrochloride, a selective 5-hydroxytryptamine 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 proliferator-activated receptor γ, fatty acid synthase and lipoprotein lipase, and downregulated sterol regulatory element-binding protein 1-c were detected in rats with streptozotocin (STZ)-induced diabetes following treatment with fluoxetine. Furthermore, fluoxetine significantly inhibited the expression levels of glucose metabolism-associated proteins in liver tissues, including glycogen synthase kinase 3β (GSK-3β), glucose-6 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 STZ-induced diabetes. Additionally, fluoxetine could inhibit the phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway, whereas LY294002, a specific inhibitor of PI3K, suppressed the function of PI3K-AKT signaling and suppressed the expression levels of glucose metabolism-associated proteins, including GSK-3β, G6PC, PEPCK and FOXO1 in BRL-3A cells. The results of the present study revealed that fluoxetine may regulate glucose and lipid metabolism via the PI3K-AKT signaling pathway in diabetic rats.
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spelling pubmed-74534942020-08-31 Fluoxetine regulates glucose and lipid metabolism via the PI3K-AKT signaling pathway in diabetic rats Yang, Hailong Cao, Qiuyun Xiong, Xiaolu Zhao, Peng Shen, Diwen Zhang, Yuzhe Zhang, Ning Mol Med Rep Articles Diabetes mellitus poses a major threat towards global heath due to a lack of effective treatment. Fluoxetine hydrochloride, a selective 5-hydroxytryptamine 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 proliferator-activated receptor γ, fatty acid synthase and lipoprotein lipase, and downregulated sterol regulatory element-binding protein 1-c were detected in rats with streptozotocin (STZ)-induced diabetes following treatment with fluoxetine. Furthermore, fluoxetine significantly inhibited the expression levels of glucose metabolism-associated proteins in liver tissues, including glycogen synthase kinase 3β (GSK-3β), glucose-6 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 STZ-induced diabetes. Additionally, fluoxetine could inhibit the phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway, whereas LY294002, a specific inhibitor of PI3K, suppressed the function of PI3K-AKT signaling and suppressed the expression levels of glucose metabolism-associated proteins, including GSK-3β, G6PC, PEPCK and FOXO1 in BRL-3A cells. The results of the present study revealed that fluoxetine may regulate glucose and lipid metabolism via the PI3K-AKT signaling pathway in diabetic rats. D.A. Spandidos 2020-10 2020-08-04 /pmc/articles/PMC7453494/ /pubmed/32945450 http://dx.doi.org/10.3892/mmr.2020.11416 Text en Copyright: © Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Yang, Hailong
Cao, Qiuyun
Xiong, Xiaolu
Zhao, Peng
Shen, Diwen
Zhang, Yuzhe
Zhang, Ning
Fluoxetine regulates glucose and lipid metabolism via the PI3K-AKT signaling pathway in diabetic rats
title Fluoxetine regulates glucose and lipid metabolism via the PI3K-AKT signaling pathway in diabetic rats
title_full Fluoxetine regulates glucose and lipid metabolism via the PI3K-AKT signaling pathway in diabetic rats
title_fullStr Fluoxetine regulates glucose and lipid metabolism via the PI3K-AKT signaling pathway in diabetic rats
title_full_unstemmed Fluoxetine regulates glucose and lipid metabolism via the PI3K-AKT signaling pathway in diabetic rats
title_short Fluoxetine regulates glucose and lipid metabolism via the PI3K-AKT signaling pathway in diabetic rats
title_sort fluoxetine regulates glucose and lipid metabolism via the pi3k-akt signaling pathway in diabetic rats
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453494/
https://www.ncbi.nlm.nih.gov/pubmed/32945450
http://dx.doi.org/10.3892/mmr.2020.11416
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