ArticleCell metabolism2014
Hepatic oxidative stress promotes insulin-STAT-5 signaling and obesity by inactivating protein tyrosine phosphatase N2.
Article in Cell metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 108 citations in OpenAlex.
- Molecular Mechanisms and Targeted Therapies of PTPN2 in Metabolic Diseases: A Review.Biomolecules · 2026Review
- Disease-associated mutations in the STAT5B SH2 domain reprogram hepatic cholesterol and lipid metabolism.Endocrinology · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Renoprotective effect of polyphenolic-rich extract of Phyllanthus niruri in streptozotocin-induced diabetic nephropathy via moderation of oxidative stress and inhibition of kidney injury.Journal of molecular histology · 2025Article
- Disease-associated mutations in the STAT5B SH2 domain reprogram hepatic cholesterol and lipid metabolism.bioRxiv : the preprint server for biology · 2025Article
- Metabolic dysfunction-associated steatohepatitis reduces hepatic HRedox biology · 2025Article
- STAT Signature Dish: Serving Immunity with a Side of Dietary Control.Biomolecules · 2025Review
- Review
- Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice.Nature communications · 2025Article
- Inflammation in glomerular diseases.Frontiers in immunology · 2025Review
- Review
- PTPRK regulates glycolysis and de novo lipogenesis to promote hepatocyte metabolic reprogramming in obesity.Nature communications · 2024Article
- Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases.Acta pharmaceutica Sinica. B · 2024Review
- A crucial role of adenosine deaminase in regulating gluconeogenesis in mice.The Journal of biological chemistry · 2024Article
- A Narrative Review of Diabetic Macroangiopathy: From Molecular Mechanism to Therapeutic Approaches.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2024Review
- The oncogenic mechanisms of the Janus kinase-signal transducer and activator of transcription pathway in digestive tract tumors.Cell communication and signaling : CCS · 2024Review
- Mechanisms of hepatic steatosis in chickens: integrated analysis of the host genome, molecular phenomics and gut microbiome.GigaScience · 2024Article
- Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis.Mediators of inflammation · 2024Article
- Targeting Protein Phosphatases for the Treatment of Chronic Liver Disease.Current drug targets · 2024Review
- Mitochondria- and NOX4-dependent antioxidant defense mitigates progression to nonalcoholic steatohepatitis in obesity.The Journal of clinical investigation · 2023Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Hepatic insulin resistance is a key contributor to the pathogenesis of obesity and type 2 diabetes (T2D). Paradoxically, the development of insulin resistance in the liver is not universal, but pathway selective, such that insulin fails to suppress gluconeogenesis but promotes lipogenesis, contributing to the hyperglycemia, steatosis, and hypertriglyceridemia that underpin the deteriorating glucose control and microvascular complications in T2D. The molecular basis for the pathway-specific insulin resistance remains unknown. Here we report that oxidative stress accompanying obesity inactivates protein-tyrosine phosphatases (PTPs) in the liver to activate select signaling pathways that exacerbate disease progression. In obese mice, hepatic PTPN2 (TCPTP) inactivation promoted lipogenesis and steatosis and insulin-STAT-5 signaling. The enhanced STAT-5 signaling increased hepatic IGF-1 production, which suppressed central growth hormone release and exacerbated the development of obesity and T2D. Our studies define a mechanism for the development of selective insulin resistance with wide-ranging implications for diseases characterized by oxidative stress.
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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.