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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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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. |
format | Online Article Text |
id | pubmed-7453494 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
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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