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FoxO1 as a tissue-specific therapeutic target for type 2 diabetes

Forkhead box O (FoxO) proteins are transcription factors that mediate many aspects of physiology and thus have been targeted as therapeutics for several diseases including metabolic disorders such as type 2 diabetes mellitus (T2D). The role of FoxO1 in metabolism has been well studied, but recently...

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Autores principales: Teaney, Nicole A., Cyr, Nicole E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629996/
https://www.ncbi.nlm.nih.gov/pubmed/37941908
http://dx.doi.org/10.3389/fendo.2023.1286838
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author Teaney, Nicole A.
Cyr, Nicole E.
author_facet Teaney, Nicole A.
Cyr, Nicole E.
author_sort Teaney, Nicole A.
collection PubMed
description Forkhead box O (FoxO) proteins are transcription factors that mediate many aspects of physiology and thus have been targeted as therapeutics for several diseases including metabolic disorders such as type 2 diabetes mellitus (T2D). The role of FoxO1 in metabolism has been well studied, but recently FoxO1’s potential for diabetes prevention and therapy has been debated. For example, studies have shown that increased FoxO1 activity in certain tissue types contributes to T2D pathology, symptoms, and comorbidities, yet in other tissue types elevated FoxO1 has been reported to alleviate symptoms associated with diabetes. Furthermore, studies have reported opposite effects of active FoxO1 in the same tissue type. For example, in the liver, FoxO1 contributes to T2D by increasing hepatic glucose production. However, FoxO1 has been shown to either increase or decrease hepatic lipogenesis as well as adipogenesis in white adipose tissue. In skeletal muscle, FoxO1 reduces glucose uptake and oxidation, promotes lipid uptake and oxidation, and increases muscle atrophy. While many studies show that FoxO1 lowers pancreatic insulin production and secretion, others show the opposite, especially in response to oxidative stress and inflammation. Elevated FoxO1 in the hypothalamus increases the risk of developing T2D. However, increased FoxO1 may mitigate Alzheimer’s disease, a neurodegenerative disease strongly associated with T2D. Conversely, accumulating evidence implicates increased FoxO1 with Parkinson’s disease pathogenesis. Here we review FoxO1’s actions in T2D conditions in metabolic tissues that abundantly express FoxO1 and highlight some of the current studies targeting FoxO1 for T2D treatment.
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spelling pubmed-106299962023-11-08 FoxO1 as a tissue-specific therapeutic target for type 2 diabetes Teaney, Nicole A. Cyr, Nicole E. Front Endocrinol (Lausanne) Endocrinology Forkhead box O (FoxO) proteins are transcription factors that mediate many aspects of physiology and thus have been targeted as therapeutics for several diseases including metabolic disorders such as type 2 diabetes mellitus (T2D). The role of FoxO1 in metabolism has been well studied, but recently FoxO1’s potential for diabetes prevention and therapy has been debated. For example, studies have shown that increased FoxO1 activity in certain tissue types contributes to T2D pathology, symptoms, and comorbidities, yet in other tissue types elevated FoxO1 has been reported to alleviate symptoms associated with diabetes. Furthermore, studies have reported opposite effects of active FoxO1 in the same tissue type. For example, in the liver, FoxO1 contributes to T2D by increasing hepatic glucose production. However, FoxO1 has been shown to either increase or decrease hepatic lipogenesis as well as adipogenesis in white adipose tissue. In skeletal muscle, FoxO1 reduces glucose uptake and oxidation, promotes lipid uptake and oxidation, and increases muscle atrophy. While many studies show that FoxO1 lowers pancreatic insulin production and secretion, others show the opposite, especially in response to oxidative stress and inflammation. Elevated FoxO1 in the hypothalamus increases the risk of developing T2D. However, increased FoxO1 may mitigate Alzheimer’s disease, a neurodegenerative disease strongly associated with T2D. Conversely, accumulating evidence implicates increased FoxO1 with Parkinson’s disease pathogenesis. Here we review FoxO1’s actions in T2D conditions in metabolic tissues that abundantly express FoxO1 and highlight some of the current studies targeting FoxO1 for T2D treatment. Frontiers Media S.A. 2023-10-23 /pmc/articles/PMC10629996/ /pubmed/37941908 http://dx.doi.org/10.3389/fendo.2023.1286838 Text en Copyright © 2023 Teaney and Cyr https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Teaney, Nicole A.
Cyr, Nicole E.
FoxO1 as a tissue-specific therapeutic target for type 2 diabetes
title FoxO1 as a tissue-specific therapeutic target for type 2 diabetes
title_full FoxO1 as a tissue-specific therapeutic target for type 2 diabetes
title_fullStr FoxO1 as a tissue-specific therapeutic target for type 2 diabetes
title_full_unstemmed FoxO1 as a tissue-specific therapeutic target for type 2 diabetes
title_short FoxO1 as a tissue-specific therapeutic target for type 2 diabetes
title_sort foxo1 as a tissue-specific therapeutic target for type 2 diabetes
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629996/
https://www.ncbi.nlm.nih.gov/pubmed/37941908
http://dx.doi.org/10.3389/fendo.2023.1286838
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