ArticleDigestive diseases and sciences2017
Activation of Insulin-PI3K/Akt-p70S6K Pathway in Hepatic Stellate Cells Contributes to Fibrosis in Nonalcoholic Steatohepatitis.
Article in Digestive diseases and sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- From mechanisms to anti-fibrotic drugs in hepatic stellate cell research: a global bibliometric analysis with patent and clinical perspectives (2000-2025).Frontiers in pharmacology · 2025Pooled it
- Metabolic drivers of MASLD and MASH: from hormonal imbalance to fibrosis.Diabetologia · 2026Review
- Neutrophil extracellular Trap-related genes in NAFLD: Biomarkers and therapeutic targets.Clinical and experimental medicine · 2026Article
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- TEAD4-mediated upregulation of LPAR3 augments hepatic stellate cell activation in portal hypertension.Cell biology and toxicology · 2025Article
- Association between metabolic associated fatty liver disease and HCC risk after SVR in HCV patients: A systematic review and meta-analysis.Clinical and experimental hepatology · 2025Article
- Insulin receptor responsiveness governs TGFβ-induced hepatic stellate cell activation: Insulin resistance instigates liver fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Circular RNAs in Liver Diseases.Advances in experimental medicine and biology · 2025Review
- Diverting hepatic lipid fluxes with lifestyles revision and pharmacological interventions as a strategy to tackle steatotic liver disease (SLD) and hepatocellular carcinoma (HCC).Nutrition & metabolism · 2024Review
- Insulin Resistance/Sensitivity Measures as Screening Indicators of Metabolic-Associated Fatty Liver Disease and Liver Fibrosis.Digestive diseases and sciences · 2024Article
- Article
- Hepatic insulin receptor: new views on the mechanisms of liver disease.Metabolism: clinical and experimental · 2023Review
- Stromal inflammation, fibrosis and cancer: An old intuition with promising potential.World journal of clinical oncology · 2023Review
- Pathophysiology of obesity and its associated diseases.Acta pharmaceutica Sinica. B · 2023Review
- Regulatory Functions and Mechanisms of Circular RNAs in Hepatic Stellate Cell Activation and Liver Fibrosis.Cells · 2023Review
- Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis.Clinical and molecular hepatology · 2023Review
- Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm.International journal of molecular sciences · 2022Review
- Hepatic kinome atlas: An in-depth identification of kinase pathways in liver fibrosis of humans and rodents.Hepatology (Baltimore, Md.) · 2022Article
- Insulin Therapy is Associated With Increased Myocardial Interstitial Fibrosis and Cardiomyocyte Apoptosis in a Rodent Model of Experimental Diabetes.Frontiers in physiology · 2022Article
- MicroRNA-122-5p Inhibition Improves Inflammation and Oxidative Stress Damage in Dietary-Induced Non-alcoholic Fatty Liver Disease Through Targeting FOXO3.Frontiers in physiology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsHyperinsulinemia and insulin resistance are hallmark features of nonalcoholic fatty liver disease and steatohepatitis (NASH). It remains unclear whether and how insulin contributes to the development of fibrosis in NASH. In this study, we explored insulin signaling in the regulation of hepatic stellate cell (HSC) activation and the progression of NASH-fibrosis.
methodsPhosphorylation of Akt and p70S6K were examined in primary HSC and in a rat model of NASH-fibrosis induced by high-fat and high-cholesterol diet for 24 weeks. HSC activation was analyzed for the changes in cell morphology, intracellular lipid droplets, expression of α-SMA and cell proliferation. The serum markers and histology for NASH-fibrosis were also characterized in animals.
resultsInsulin enhanced the expression of smooth muscle actin-α in quiescent but not in activated HSC in culture. Insulin-mediated activation of the PI3K/Akt-p70S6K pathway was involved in the regulation of profibrogenic effects of insulin. Although insulin did not stimulate HSC proliferation directly, the insulin-PI3K/Akt-p70S6K pathway was necessary for serum-enhanced cell proliferation during initial HSC activation. In a rat model of NASH-fibrosis induced by high-fat and high-cholesterol diet, hyperinsulinemia is associated with the activation of p70S6K and enhanced fibrosis.
conclusionThe insulin-PI3K/Akt-p70S6K pathway plays an important role in the early activation of HSC. The profibrogenic effect of insulin is dependent on the activation stage of HSC. Dysregulation of the insulin pathway likely correlates with the development of fibrosis in NASH, suggesting a potentially novel antifibrotic target of inhibiting insulin signaling in HSC.
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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 Socratic graph.