ArticleCell death & disease2016
Glucolipotoxicity initiates pancreatic β-cell death through TNFR5/CD40-mediated STAT1 and NF-κB activation.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Type 2 Diabetes: How Much of an Autoimmune Disease?Frontiers in endocrinology · 2019Pooled it
- Type 2 Diabetes Mellitus: A Metabolic Model of Accelerated Aging - Multi-Organ Mechanisms and Intervention Approaches.Aging and disease · 2025Review
- Silencing the FABP3 gene in insulin-secreting cells reduces fatty acid uptake and protects against lipotoxicity.Acta diabetologica · 2024Article
- Article
- NR3C1/Glucocorticoid receptor activation promotes pancreatic β-cell autophagy overload in response to glucolipotoxicity.Autophagy · 2023Article
- The Adaptor Protein NumbL Is Involved in the Control of Glucolipotoxicity-Induced Pancreatic Beta Cell Apoptosis.International journal of molecular sciences · 2023Article
- Research progress on the mechanism of beta-cell apoptosis in type 2 diabetes mellitus.Frontiers in endocrinology · 2022Review
- Analysis of co-expression gene network associated with intracranial aneurysm and type 2 diabetes mellitus.Frontiers in neurology · 2022Article
- Lipid-Induced Adaptations of the Pancreatic Beta-Cell to Glucotoxic Conditions Sustain Insulin Secretion.International journal of molecular sciences · 2021Review
- Hepatic-Metabolite-Based Intermittent Fasting Enables a Sustained Reduction in Insulin Resistance in Type 2 Diabetes and Metabolic Syndrome.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2021Article
- Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies.International journal of molecular sciences · 2021Review
- Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells.International journal of molecular sciences · 2021Review
- Protein Kinases Signaling in Pancreatic Beta-cells Death and Type 2 Diabetes.Advances in experimental medicine and biology · 2021Article
- Nutrient Sensor mTOR and OGT: Orchestrators of Organelle Homeostasis in PancreaticJournal of diabetes research · 2020Review
- Yunvjian-Medicated Serum Protects INS-1 Cells against Glucolipotoxicity-Induced Apoptosis through Autophagic Flux Modulation.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Liraglutide protects against glucolipotoxicity-induced RIN-m5F β-cell apoptosis through restoration of PDX1 expression.Journal of cellular and molecular medicine · 2019Article
- LncRNA LEGLTBC Functions as a ceRNA to Antagonize the Effects of miR-34a on the Downregulation of SIRT1 in Glucolipotoxicity-Induced INS-1 Beta Cell Oxidative Stress and Apoptosis.Oxidative medicine and cellular longevity · 2019Article
- Temporal Proteomic Analysis of Pancreatic β-Cells in Response to Lipotoxicity and Glucolipotoxicity.Molecular & cellular proteomics : MCP · 2018Article
- Identification of key gene pathways and coexpression networks of islets in human type 2 diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2018Article
- Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions.Current topics in medicinal chemistry · 2018Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes is a chronic metabolic disorder, where failure to maintain normal glucose homoeostasis is associated with, and exacerbated by, obesity and the concomitant-elevated free fatty acid concentrations typically found in these patients. Hyperglycaemia and hyperlipidaemia together contribute to a decline in insulin-producing β-cell mass through activation of the transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)-1. There are however a large number of molecules potentially able to modulate NF-κB and STAT1 activity, and the mechanism(s) by which glucolipotoxicity initially induces NF-κB and STAT1 activation is currently poorly defined. Using high-density microarray analysis of the β-cell transcritptome, we have identified those genes and proteins most sensitive to glucose and fatty acid environment. Our data show that of those potentially able to activate STAT1 or NF-κB pathways, tumour necrosis factor receptor (TNFR)-5 is the most highly upregulated by glucolipotoxicity. Importantly, our data also show that the physiological ligand for TNFR5, CD40L, elicits NF-κB activity in β-cells, whereas selective knockdown of TNFR5 ameliorates glucolipotoxic induction of STAT1 expression and NF-κB activity. This data indicate for the first time that TNFR5 signalling has a major role in triggering glucolipotoxic islet cell death.
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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.