ArticleNature communications2014
Integrated control of hepatic lipogenesis versus glucose production requires FoxO transcription factors.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
What it found
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Who cites it
125 citing papers in PubMed, 185 citations in OpenAlex.
- Gastric bypass surgery with exercise alters plasma microRNAs that predict improvements in cardiometabolic risk.International journal of obesity (2005) · 2017Trial
- mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation.Science advances · 2026Article
- FoxO transcription factors coordinate the urea cycle and gluconeogenesis by controllingiScience · 2026Article
- Manganese availability determines insulin sensitivity by enhancing Akt activity.bioRxiv : the preprint server for biology · 2026Article
- Hepatic FGF21 is not required for fasting metabolism but guides protein appetite post energy depletion.EMBO reports · 2026Article
- Beneficial Effects of Gegen Qinlian Decoction and Its Food-Medicine Homologous Alternative Formulas Against Type 2 Diabetes Mellitus: Insights from Multi-Omics Analysis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- FOXO: a key target in regulating aging and age-related diseases.Biogerontology · 2026Review
- FoxO1 signaling in B cell malignancies and its therapeutic targeting.FEBS letters · 2025Review
- Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications.Diabetes & metabolism journal · 2025Review
- Insulin resistance in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- Identification and Functional Analysis of Key microRNAs in the Early Extrauterine Environmental Adaptation of Piglets.International journal of molecular sciences · 2025Article
- The endocrine role of hepatokines: implications for human health and disease.Frontiers in endocrinology · 2025Review
- Targeting the PI3K/AKT signaling pathway: an important molecular mechanism of herbal medicine in the treatment of MASLD/MASH.Frontiers in nutrition · 2025Review
- The role of insulin signaling with FOXO and FOXK transcription factors.Endocrine journal · 2024Review
- Hepatic WDR23 proteostasis mediates insulin homeostasis by regulating insulin-degrading enzyme capacity.GeroScience · 2024Article
- Embryonic Leucine Promotes Early Postnatal Growth via mTOR Signalling in Japanese Quails.Animals : an open access journal from MDPI · 2024Article
- The role of adipose tissue dysfunction in hepatic insulin resistance and T2D.The Journal of endocrinology · 2024Review
- Review
- The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity.Antioxidants (Basel, Switzerland) · 2024Review
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Insulin integrates hepatic glucose and lipid metabolism, directing nutrients to storage as glycogen and triglyceride. In type 2 diabetes, levels of the former are low and the latter are exaggerated, posing a pathophysiologic and therapeutic conundrum. A branching model of insulin signalling, with FoxO1 presiding over glucose production and Srebp-1c regulating lipogenesis, provides a potential explanation. Here we illustrate an alternative mechanism that integrates glucose production and lipogenesis under the unifying control of FoxO. Liver-specific ablation of three FoxOs (L-FoxO1,3,4) prevents the induction of glucose-6-phosphatase and the repression of glucokinase during fasting, thus increasing lipogenesis at the expense of glucose production. We document a similar pattern in the early phases of diet-induced insulin resistance, and propose that FoxOs are required to enable the liver to direct nutritionally derived carbons to glucose versus lipid metabolism. Our data underscore the heterogeneity of hepatic insulin resistance during progression from the metabolic syndrome to overt diabetes, and the conceptual challenge of designing therapies that curtail glucose production without promoting hepatic lipid accumulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.