ArticleJournal of virology2008
Hepatitis C virus core protein upregulates serine phosphorylation of insulin receptor substrate-1 and impairs the downstream akt/protein kinase B signaling pathway for insulin resistance.
Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing.Hepatology international · 2016Guideline
- Antiviral therapy and the risk of extrahepatic malignancies in chronic hepatitis C: insights from recent evidence.Translational cancer research · 2026Article
- Hepatitis C Virus and Type 2 Diabetes: Mechanisms, Clinical Impact, and Post-DAA Management.Journal of medical virology · 2026Review
- Review
- Extrahepatic Cancer Risk in Patients with Hepatitis C Virus Infection Treated with Direct-Acting Antivirals.Microorganisms · 2024Review
- Review
- The association between plasma free amino acids and type 2 diabetes mellitus complicated with infection in Chinese patients.Diabetology & metabolic syndrome · 2024Article
- Observational
- Seroprevalence and associated risk factors of hepatitis C infection among diabetic patients in South-Kivu, Eastern Democratic Republic of the Congo: A cross-sectional study.Health science reports · 2023Article
- ANGPTL4 is a potential driver of HCV-induced peripheral insulin resistance.Scientific reports · 2023Article
- Molecular Mechanisms, Diagnosis and Treatments in Digestive Malignancy.International journal of molecular sciences · 2023Article
- The Effects of Viruses on Insulin Sensitivity and Blood-Brain Barrier Function.International journal of molecular sciences · 2023Review
- Article
- Signaling Induced by Chronic Viral Hepatitis: Dependence and Consequences.International journal of molecular sciences · 2022Review
- Article
- Impact of HCV infection and ethnicity on incident type 2 diabetes: findings from a large population-based cohort in British Columbia.BMJ open diabetes research & care · 2021Article
- Sofosbuvir improves HCV-induced insulin resistance by blocking IRS1 degradation.Clinical and translational medicine · 2021Article
- Virus Elimination by Direct-Acting Antiviral Agents Impacts Glucose Homeostasis in Chronic Hepatitis C Patients.Frontiers in endocrinology · 2021Observational
- Cell fate, metabolic reprogramming and lncRNA of tumor-initiating stem-like cells induced by alcohol.Chemico-biological interactions · 2020Review
- Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis.International journal of molecular sciences · 2019Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Chronic hepatitis C virus (HCV) infection has a significantly increased prevalence of type 2 diabetes mellitus (T2DM). Insulin resistance is a critical component of T2DM pathogenesis. Several mechanisms are likely to be involved in the pathogenesis of HCV-related insulin resistance. Since we and others have previously observed that HCV core protein activates c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase, we examined the contribution of these pathways to insulin resistance in hepatocytes. Our experimental findings suggest that HCV core protein alone or in the presence of other viral proteins increases Ser(312) phosphorylation of the insulin receptor substrate-1 (IRS-1). Hepatocytes infected with cell culture-grown HCV genotype 1a or 2a displayed a significant increase in the Ser(473) phosphorylation status of the Ser/Thr kinase protein kinase B (Akt/PKB), while Thr(308) phosphorylation was not significantly altered. HCV core protein-mediated Ser(312) phosphorylation of IRS-1 was inhibited by JNK (SP600125) and phosphatidylinositol-3 kinase (LY294002) inhibitors. A functional assay also suggested that hepatocytes expressing HCV core protein alone or infected with cell culture-grown HCV exhibited a suppression of 2-deoxy-d-[(3)H]glucose uptake. Inhibition of the JNK signaling pathway significantly restored glucose uptake despite HCV core expression in hepatocytes. Taken together, our results demonstrated that HCV core protein increases IRS-1 phosphorylation at Ser(312) which may contribute in part to the mechanism of insulin resistance.
Indexed as
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What OpenQuestion holds
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.