ArticleThe Journal of clinical investigation2007
Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 266 papers.
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Who cites it
266 citing papers in PubMed, 477 citations in OpenAlex.
- The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans.The Journal of clinical investigation · 2012Trial
- Reversal of muscle insulin resistance by weight reduction in young, lean, insulin-resistant offspring of parents with type 2 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2012 · on this mapTrial
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- Integrated analysis of insulin resistance reveals metabolic remodeling following diet switch-triggered calorie reduction.Science advances · 2026Article
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- Gamma oryzanol modulates hepatic lipids expression and regulates integrated pathways in liver disease pathophysiology under a high sugar fat diet.Scientific reports · 2025Article
- Emerging Roles of Post-Translational Modifications in Metabolic Homeostasis and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways.Clinical science (London, England : 1979) · 2025Review
- Resveratrol Impairs Insulin Signaling in Hepatic Cells via Activation of PKC and PTP1B Pathways.International journal of molecular sciences · 2025Article
- Effects of Tinospora cordifolia (giloy) on metabolic syndrome components: a mechanistic review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Plasma Lipid Metabolites, Clinical Glycemic Predictors, and Incident Type 2 Diabetes.Diabetes care · 2025Article
- Physiological and pathophysiological actions of insulin in the liver.Endocrine journal · 2025Review
- High-fat-diet-induced hepatic insulin resistanceiScience · 2024Article
- Association Between Ultraprocessed Food Consumption and Metabolic Disorders in Children and Adolescents with Obesity.Nutrients · 2024Article
206 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Nonalcoholic fatty liver disease is strongly associated with hepatic insulin resistance and type 2 diabetes mellitus, but the molecular signals linking hepatic fat accumulation to hepatic insulin resistance are unknown. Three days of high-fat feeding in rats results specifically in hepatic steatosis and hepatic insulin resistance. In this setting, PKCepsilon, but not other isoforms of PKC, is activated. To determine whether PKCepsilon plays a causal role in the pathogenesis of hepatic insulin resistance, we treated rats with an antisense oligonucleotide against PKCepsilon and subjected them to 3 days of high-fat feeding. Knocking down PKCepsilon expression protects rats from fat-induced hepatic insulin resistance and reverses fat-induced defects in hepatic insulin signaling. Furthermore, we show that PKCepsilon associates with the insulin receptor in vivo and impairs insulin receptor kinase activity both in vivo and in vitro. These data support the hypothesis that PKCepsilon plays a critical role in mediating fat-induced hepatic insulin resistance and represents a novel therapeutic target for type 2 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.