ArticleNature communications2016
The MDM2-p53-pyruvate carboxylase signalling axis couples mitochondrial metabolism to glucose-stimulated insulin secretion in pancreatic β-cells.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Cross-Study Meta-Analysis of Blood Transcriptomes in Type 2 Diabetes.International journal of molecular sciences · 2025Pooled it
- CBX4 stabilizes NEUROD1 through SUMO-ubiquitin crosstalk to delay β-cell senescence.Nature communications · 2026Article
- Bioengineered systems to exploit tumor microenvironment metabolism.Trends in cancer · 2026Review
- β-cell FMO3-produced TMAO prevents NF-κB-mediated senescence and inflammation in ageing and diabetic conditions.Nature communications · 2026Article
- Liver-specific delivery of MDM2 antisense oligonucleotides counteracts diet-induced metabolic-dysfunction-associated steatotic liver diseases.Molecular therapy. Nucleic acids · 2026Article
- Branched-chain α-keto acids impair glucose-stimulated insulin secretion in pancreatic β-cells under diabetes by reactivating the LDHA-lactate axis.Nature communications · 2026Article
- Soybean oil and leucine in late gestation and lactation improve maternal and offspring lipid metabolism and insulin sensitivity: insights from pig model.Frontiers in veterinary science · 2026Article
- Uric Acid Causes Pancreatic β Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress Pathways.Diseases (Basel, Switzerland) · 2025Article
- Metabolic regulation by p53: Implications for cancer therapy.Molecules and cells · 2025Review
- The mitochondrial enzyme pyruvate carboxylase restricts pancreatic β-cell senescence by blocking p53 activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- MDM2 induces pro-inflammatory and glycolytic responses in M1 macrophages by integrating iNOS-nitric oxide and HIF-1α pathways in mice.Nature communications · 2024Article
- Pyruvate Carboxylase Attenuates Myocardial Ischemia-Reperfusion Injury in Heart Transplantation via Wnt/β-Catenin-Mediated Glutamine Metabolism.Biomedicines · 2024Article
- Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.Metabolites · 2024Review
- Ubiquitination and Metabolic Disease.Advances in experimental medicine and biology · 2024Review
- Failure to repair endogenous DNA damage in β-cells causes adult-onset diabetes in mice.Aging biology · 2023Article
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Adipose methylome integrative-omic analyses reveal genetic and dietary metabolic health drivers and insulin resistance classifiers.Genome medicine · 2022Article
- Hepatic MDM2 Causes Metabolic Associated Fatty Liver Disease by Blocking Triglyceride-VLDL Secretion via ApoB Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Melatonin protects against nonylphenol caused pancreatic β-cells damage through MDM2-P53-P21 axis.Toxicology research · 2022Article
- β-Klotho promotes glycolysis and glucose-stimulated insulin secretion via GP130.Nature metabolism · 2022Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial metabolism is pivotal for glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells. However, little is known about the molecular machinery that controls the homeostasis of intermediary metabolites in mitochondria. Here we show that the activation of p53 in β-cells, by genetic deletion or pharmacological inhibition of its negative regulator MDM2, impairs GSIS, leading to glucose intolerance in mice. Mechanistically, p53 activation represses the expression of the mitochondrial enzyme pyruvate carboxylase (PC), resulting in diminished production of the TCA cycle intermediates oxaloacetate and NADPH, and impaired oxygen consumption. The defective GSIS and mitochondrial metabolism in MDM2-null islets can be rescued by restoring PC expression. Under diabetogenic conditions, MDM2 and p53 are upregulated, whereas PC is reduced in mouse β-cells. Pharmacological inhibition of p53 alleviates defective GSIS in diabetic islets by restoring PC expression. Thus, the MDM2-p53-PC signalling axis links mitochondrial metabolism to insulin secretion and glucose homeostasis, and could represent a therapeutic target in diabetes.
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