ArticleMolecular and cellular biology2016
Novel Grb14-Mediated Cross Talk between Insulin and p62/Nrf2 Pathways Regulates Liver Lipogenesis and Selective Insulin Resistance.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- Lipedema: Progress, Challenges, and the Road Ahead.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Pooled it
- Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease.Nature genetics · 2023Pooled it
- Complementary structure of statistical significance and predictive relevance in explainable machine learning-based transcriptomic tissue classification of Hanwoo cattle.Frontiers in genetics · 2026Article
- Article
- Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression.Nature communications · 2024Article
- RREB1 regulates neuronal proteostasis and the microtubule network.Science advances · 2024Article
- Mechanism of Action and Related Natural Regulators of Nrf2 in Nonalcoholic Fatty Liver Disease.Current drug delivery · 2024Review
- Article
- Metabolic Effects of the Waist-To-Hip Ratio Associated LocusInternational journal of molecular sciences · 2022Article
- The Antarctic Weddell seal genome reveals evidence of selection on cardiovascular phenotype and lipid handling.Communications biology · 2022Article
- Causal associations of waist circumference and waist-to-hip ratio with type II diabetes mellitus: new evidence from Mendelian randomization.Molecular genetics and genomics : MGG · 2021Article
- Characterization of Exome Variants and Their Metabolic Impact in 6,716 American Indians from the Southwest US.American journal of human genetics · 2020Article
- Inhibition of Grb14, a negative modulator of insulin signaling, improves glucose homeostasis without causing cardiac dysfunction.Scientific reports · 2020Article
- Lipid mediators of insulin signaling in diabetic kidney disease.American journal of physiology. Renal physiology · 2019Review
- A coding and non-coding transcriptomic perspective on the genomics of human metabolic disease.Nucleic acids research · 2018Article
- NRF2 and the Hallmarks of Cancer.Cancer cell · 2018Review
- Nuclear lamina genetic variants, including a truncated LAP2, in twins and siblings with nonalcoholic fatty liver disease.Hepatology (Baltimore, Md.) · 2018Article
- p62/SQSTM1-Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer.FEBS letters · 2016Review
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A long-standing paradox in the pathophysiology of metabolic diseases is the selective insulin resistance of the liver. It is characterized by a blunted action of insulin to reduce glucose production, contributing to hyperglycemia, while de novo lipogenesis remains insulin sensitive, participating in turn to hepatic steatosis onset. The underlying molecular bases of this conundrum are not yet fully understood. Here, we established a model of selective insulin resistance in mice by silencing an inhibitor of insulin receptor catalytic activity, the growth factor receptor binding protein 14 (Grb14) in liver. Indeed, Grb14 knockdown enhanced hepatic insulin signaling but also dramatically inhibited de novo fatty acid synthesis. In the liver of obese and insulin-resistant mice, downregulation of Grb14 markedly decreased blood glucose and improved liver steatosis. Mechanistic analyses showed that upon Grb14 knockdown, the release of p62/sqstm1, a partner of Grb14, activated the transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2), which in turn repressed the lipogenic nuclear liver X receptor (LXR). Our study reveals that Grb14 acts as a new signaling node that regulates lipogenesis and modulates insulin sensitivity in the liver by acting at a crossroad between the insulin receptor and the p62-Nrf2-LXR signaling pathways.
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