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Cited by 436

The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism

Open access
Matsumoto, M.·2006·Journal of Clinical Investigation

Abstract

Hepatic insulin resistance affects both carbohydrate and lipid metabolism. It has been proposed that insulin controls these 2 metabolic branches through distinct signaling pathways. FoxO transcription factors are considered effectors of the pathway regulating hepatic glucose production. Here we show that adenoviral delivery of constitutively nuclear forkhead box O1 (FoxO1) to mouse liver results in steatosis arising from increased triglyceride accumulation and decreased fatty acid oxidation. FoxO1 gain of function paradoxically increased insulin sensitivity by promoting Akt phosphorylation, while FoxO1 inhibition via siRNA decreased it. We show that FoxO1 regulation of Akt phosphorylation does not require DNA binding and is associated with repression of the pseudokinase tribble 3 (Trb3), a modulator of Akt activity. This unexpected dual role of FoxO1 in promoting insulin sensitivity and lipid synthesis in addition to glucose production has the potential to explain the peculiar admixture of insulin resistance and sensitivity that is commonly observed in the metabolic syndrome.

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Metadata

Authors
Matsumoto, M.
Venue
Journal of Clinical Investigation
Published
2006-08-10
Volume
116
Issue
9
Pages
2464-72
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2080863734
Cited by
436
References
9
FWCI
8.35
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism. https://app.cochat.ai/papers/10.1172/jci27047
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Matsumoto, M. (2006). Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism. Journal of Clinical Investigation. https://doi.org/10.1172/jci27047

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.