ArticleDiabetes2012
Hepatocyte-specific Ptpn6 deletion protects from obesity-linked hepatic insulin resistance.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease.Nature communications · 2024Article
- Vanadium Complexes with Thioanilide Derivatives of Amino Acids: Inhibition of Human Phosphatases and Specificity in Various Cell Models of Metabolic Disturbances.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Regulation of PPARγ2 Stability and Activity by SHP-1.Molecular and cellular biology · 2024Article
- A novel combination of sitagliptin and melatonin ameliorates T2D manifestations: studies on experimental diabetic models.Journal of endocrinological investigation · 2023Article
- Dual PTP1B/TC-PTP Inhibitors: Biological Evaluation of 3-(Hydroxymethyl)cinnoline-4(International journal of molecular sciences · 2023Article
- Oxidative stress in obesity-associated hepatocellular carcinoma: sources, signaling and therapeutic challenges.Oncogene · 2021Review
- Phloretin attenuates STAT-3 activity and overcomes sorafenib resistance targeting SHP-1-mediated inhibition of STAT3 and Akt/VEGFR2 pathway in hepatocellular carcinoma.Cell communication and signaling : CCS · 2019Article
- Targeted SHP-1 Silencing Modulates the Macrophage Phenotype, Leading to Metabolic Improvement in Dietary Obese Mice.Molecular therapy. Nucleic acids · 2019Article
- The HNF1α-regulated lncRNA HNF1A-AS1 reverses the malignancy of hepatocellular carcinoma by enhancing the phosphatase activity of SHP-1.Molecular cancer · 2018Article
- SVMRFE based approach for prediction of most discriminatory gene target for type II diabetes.Genomics data · 2017Article
- Hepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia.Scientific reports · 2017Article
- SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes.Diabetologia · 2017Article
- Hepatocyte glutathione peroxidase-1 deficiency improves hepatic glucose metabolism and decreases steatohepatitis in mice.Diabetologia · 2016Article
- Inhibition of Src homology 2 domain-containing phosphatase 1 increases insulin sensitivity in high-fat diet-induced insulin-resistant mice.FEBS open bio · 2016Article
- An HNF1α-regulated feedback circuit modulates hepatic fibrogenesis via the crosstalk between hepatocytes and hepatic stellate cells.Cell research · 2015Article
- Enhanced insulin signaling in density-enhanced phosphatase-1 (DEP-1) knockout mice.Molecular metabolism · 2015Article
- Protectin DX alleviates insulin resistance by activating a myokine-liver glucoregulatory axis.Nature medicine · 2014Article
- Metabolic regulation by protein tyrosine phosphatases.Journal of biomedical research · 2014Article
- Role of protein tyrosine phosphatases in the modulation of insulin signaling and their implication in the pathogenesis of obesity-linked insulin resistance.Reviews in endocrine & metabolic disorders · 2014Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The protein-tyrosine phosphatase Shp1 negatively regulates insulin action on glucose homeostasis in liver and muscle, but its potential role in obesity-linked insulin resistance has not been examined. To investigate the role of Shp1 in hepatic insulin resistance, we generated hepatocyte-specific Shp1 knockout mice (Ptpn6(H-KO)), which were subjected to extensive metabolic monitoring throughout an 8-week standard chow diet (SD) or high-fat diet (HFD) feeding. We report for the first time that Shp1 expression is upregulated in metabolic tissues of HFD-fed obese mice. When compared with their Shp1-expressing Ptpn6(f/f) littermates, Ptpn6(H-KO) mice exhibited significantly lowered fasting glycemia and heightened hepatic insulin sensitivity. After HFD feeding, Ptpn6(H-KO) mice developed comparable levels of obesity as Ptpn6(f/f) mice, but they were remarkably protected from liver insulin resistance, as revealed by euglycemic clamps and hepatic insulin signaling determinations. Although Ptpn6(H-KO) mice still acquired diet-induced peripheral insulin resistance, they were less hyperinsulinemic during a glucose tolerance test because of reduced insulin secretion. Ptpn6(H-KO) mice also exhibited increased insulin clearance in line with enhanced CC1 tyrosine phosphorylation in liver. These results show that hepatocyte Shp1 plays a critical role in the development of hepatic insulin resistance and represents a novel therapeutic target for obesity-linked diabetes.
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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.