The multifaceted function of FoxO1 in pancreatic β-cell dysfunction and insulin resistance: Therapeutic potential for type 2 diabetes

Wang, Hongyu, Bai, Ran, Wang, Yubing, Qu, Meihua, Zhou, You ORCID: https://orcid.org/0000-0002-1743-1291, Gao, Zhiqin and Wang, Yi 2025. The multifaceted function of FoxO1 in pancreatic β-cell dysfunction and insulin resistance: Therapeutic potential for type 2 diabetes. Life Sciences 364 , 123384. 10.1016/j.lfs.2025.123384 Item availability restricted.

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Abstract

The forkhead box O1 (FOXO1), the first discovered member of the FoxO family, is a critical transcription factor predominantly found in insulin-secreting and insulin-sensitive tissues. In the pancreas of adults, FoxO1 expression is restricted to islet β cells. We determined that in human islet microarray datasets, FoxO1 expression is higher than other FoxO transcription factors. Our analyses of three human islet datasets revealed that FoxO1 expression tends to shows a negative correlation with type 2 diabetes and no correlation with body mass index (BMI) between individuals with low levels of HbA (or ND, non-diabetic) and high levels of HbA (or T2D, type 2 diabetes). However, FoxO1 function is multifaceted and mainly regulated by post-translational modifications including phosphorylation and deacetylation that involved in pancreatic β cell function and insulin sensitivity. This study summarized the molecular mechanisms underlying the role of FoxO1 activity in pancreatic β-cell dysfunction and insulin resistance in T2D. In addition, we discussed the therapeutic potential of FoxO1 inhibitors in diabetes treatment. [Abstract copyright: Copyright © 2025. Published by Elsevier Inc.]

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Elsevier
ISSN:	0024-3205
Date of First Compliant Deposit:	6 February 2025
Date of Acceptance:	8 January 2025
Last Modified:	06 Feb 2025 11:00
URI:	https://orca.cardiff.ac.uk/id/eprint/175653

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