ArticleCell metabolism2023
Fructose-1,6-bisphosphatase is a nonenzymatic safety valve that curtails AKT activation to prevent insulin hyperresponsiveness.
Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
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- FBP1-Mediated Compartmentalization of Glycolytic Enzyme Complexes Suppresses PKM2 Function to Ameliorate MASLD Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- TERT drives liver tumorigenesis beyond telomere elongation.Life science alliance · 2026Article
- Gene co-expression networks related to intramuscular fatty acid composition across different pig genotypes.BMC genomics · 2026Article
- MIF-mediated crosstalk between THRSP + hepatocytes and CD74 + lipid-associated macrophages in hepatic periportal zone drives MASH.Hepatology (Baltimore, Md.) · 2026Article
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- Acute glucose stimulation drives coordinated translational reprogramming in primary pancreatic islets: from global remodeling to fine-tuned insulin synthesis.Frontiers in endocrinology · 2026Article
- TRIM36 inhibits lung fibroblast activation and pulmonary fibrosis through the degradation of phospho-AKT1.iScience · 2025Article
- Association between plasma proteomic dynamic changes and metabolic outcomes in patients undergoing bariatric surgery.International journal of obesity (2005) · 2025Article
- Crosstalk between O-GlcNAcylation and phosphorylation in metabolism: regulation and mechanism.Cell death and differentiation · 2025Review
- Moonlighting functions of glucose metabolic enzymes and metabolites in cancer.Nature reviews. Cancer · 2025Review
- S-adenosylmethionine deficit disrupts very low-density lipoprotein metabolism promoting liver lipid accumulation in mice.Journal of lipid research · 2025Article
- The FBP1-TP53-NRF2 metabolic switch in metabolic dysfunction-associated steatohepatitis-hepatocellular carcinoma progression and senescence reversal.Clinical and translational medicine · 2025Article
- SR-A3 suppresses AKT activation to protect against MAFLD by inhibiting XIAP-mediated PTEN degradation.Nature communications · 2025Article
- Targeting FDFT1 Reduces Cholesterol and Bile Acid Production and Delays Hepatocellular Carcinoma Progression Through the HNF4A/ALDOB/AKT1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Effects ofInternational journal of molecular sciences · 2025Article
- Multiomics analysis of human serum and animal experiments reveals the protective mechanism of Qingre Huoxue Decoction against rheumatoid arthritis.Frontiers in immunology · 2025Article
- Cross-Disease Identification of FBP1 in Atherosclerosis and Calcific Aortic Valve Disease via Integrated Bioinformatics and Validation: Functional Analysis and Therapeutic Target Exploration.Journal of inflammation research · 2025Article
- Article
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23 authors at 4 institutions in 2 countries.
Funding
Abstract
Insulin inhibits gluconeogenesis and stimulates glucose conversion to glycogen and lipids. How these activities are coordinated to prevent hypoglycemia and hepatosteatosis is unclear. Fructose-1,6-bisphosphatase (FBP1) is rate controlling for gluconeogenesis. However, inborn human FBP1 deficiency does not cause hypoglycemia unless accompanied by fasting or starvation, which also trigger paradoxical hepatomegaly, hepatosteatosis, and hyperlipidemia. Hepatocyte FBP1-ablated mice exhibit identical fasting-conditional pathologies along with AKT hyperactivation, whose inhibition reversed hepatomegaly, hepatosteatosis, and hyperlipidemia but not hypoglycemia. Surprisingly, fasting-mediated AKT hyperactivation is insulin dependent. Independently of its catalytic activity, FBP1 prevents insulin hyperresponsiveness by forming a stable complex with AKT, PP2A-C, and aldolase B (ALDOB), which specifically accelerates AKT dephosphorylation. Enhanced by fasting and weakened by elevated insulin, FBP1:PP2A-C:ALDOB:AKT complex formation, which is disrupted by human FBP1 deficiency mutations or a C-terminal FBP1 truncation, prevents insulin-triggered liver pathologies and maintains lipid and glucose homeostasis. Conversely, an FBP1-derived complex disrupting peptide reverses diet-induced insulin resistance.
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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.