ArticleScience (New York, N.Y.)2005
The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin.
Article in Science (New York, N.Y.), 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 892 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Adaptive Study for Efficacy and Safety of Metformin Glycinate for the Treatment of Patients With MS and DM2, Hospitalized With Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2. Randomized, Double-Blind, Phase IIIb.
Effect of Metformin in Combination With Tyrosine Kinase Inhibitors (TKI) on Clinical, Biochemical and Nutritional in Patients With Non-Small Cell Lung Carcinoma (NSCLC): Randomized Clinical Trial
Adaptive Study to Demonstrate Efficacy and Safety of Metformin Glycinate for the Treatment of Hospitalized Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2. Randomized, Double-Blind, Phase IIIb
Who cites it
892 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,930 citations in OpenAlex.
- Metformin Use on Incidence and Oncologic Outcomes of Bladder Cancer Patients With T2DM: An Updated Meta-Analysis.Frontiers in pharmacology · 2022Pooled it
- Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes.JNCI cancer spectrum · 2023 · on this mapTrial
- Effects of mulberry twig alkaloids(Sangzhi alkaloids) and metformin on blood glucose fluctuations in combination with premixed insulin-treated patients with type 2 diabetes.Frontiers in endocrinology · 2023Trial
- Effects of Behavioral Weight Loss and Metformin on IGFs in Cancer Survivors: A Randomized Trial.The Journal of clinical endocrinology and metabolism · 2021 · on this mapTrial
- Paradoxical non-catalytic kinase functions are driven by inhibitor-induced displacement of autoinhibitory domains.Molecular systems biology · 2026Article
- Targeting metabolic dysregulation in postmenopausal breast cancer: Synergistic effects of nutrition-based interventions and exercise on molecular and cellular pathways.Cancer cell international · 2026Review
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- Decreased AMP-kinase function in pulmonary artery smooth muscle cells contributes to pulmonary artery remodeling in persistent pulmonary hypertension of the newborn.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- From Metabolism to Longevity: Molecular Mechanisms Underlying Metformin's Anticancer and Anti-Aging Effects.Current issues in molecular biology · 2026Review
- Synergistic associations of metformin and GLP-1 receptor agonist use with adiposity-related cancer incidence in people living with type 2 diabetes.Diabetes, obesity & metabolism · 2026Article
- Tissue Iron Predicts Metformin Responsiveness in a Mouse Model and in Humans with Type 2 Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Research Progress on the Molecular Mechanism of Metformin Regulating AMPK Signaling Pathway in Inhibiting Liver Cancer.OncoTargets and therapy · 2026Review
- Repurposing metformin for cardioprotection: mechanisms and therapeutic potential across cardiovascular pathologies.Frontiers in pharmacology · 2026Review
- The interplay between NLRP3 inflammasome and metabolic signals in gouty arthritis.Frontiers in immunology · 2026Review
- The immunology of sepsis: translating new insights into clinical practice.Nature reviews. Nephrology · 2026Review
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Glaucoma Risk with Metformin and Sulfonylurea Therapies in Type 2 Diabetes: A Retrospective Cohort Study.Clinical ophthalmology (Auckland, N.Z.) · 2026Article
- The role of combined Metformin and pharmaceutical molecules with anti-androgenic properties in the therapy of PCOS in adult women.Endocrine · 2025Review
- The role of AMPK signaling pathway in the pathogenesis of type 2 diabetes mellitus with its complications and related metabolic disorders.Metabolism open · 2025Review
- From Diabetes to Degenerative Diseases: The Multifaceted Action of Metformin.International journal of molecular sciences · 2025Review
832 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The Peutz-Jegher syndrome tumor-suppressor gene encodes a protein-threonine kinase, LKB1, which phosphorylates and activates AMPK [adenosine monophosphate (AMP)-activated protein kinase]. The deletion of LKB1 in the liver of adult mice resulted in a nearly complete loss of AMPK activity. Loss of LKB1 function resulted in hyperglycemia with increased gluconeogenic and lipogenic gene expression. In LKB1-deficient livers, TORC2, a transcriptional coactivator of CREB (cAMP response element-binding protein), was dephosphorylated and entered the nucleus, driving the expression of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), which in turn drives gluconeogenesis. Adenoviral small hairpin RNA (shRNA) for TORC2 reduced PGC-1alpha expression and normalized blood glucose levels in mice with deleted liver LKB1, indicating that TORC2 is a critical target of LKB1/AMPK signals in the regulation of gluconeogenesis. Finally, we show that metformin, one of the most widely prescribed type 2 diabetes therapeutics, requires LKB1 in the liver to lower blood glucose levels.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.