ArticleProceedings of the National Academy of Sciences of the United States of America2015
Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.
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Who cites it
136 citing papers in PubMed, 227 citations in OpenAlex.
- Free fatty acid processing diverges in human pathologic insulin resistance conditions.The Journal of clinical investigation · 2020Trial
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- Basal insulin peglispro versus insulin glargine in insulin-naïve type 2 diabetes: IMAGINE 2 randomized trial.Diabetes, obesity & metabolism · 2016Trial
- Randomized double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 2 diabetes: IMAGINE 4.Diabetes, obesity & metabolism · 2016Trial
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- Amphibian Skin-Derived Peptides as Emerging Therapeutic Scaffolds for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Pharmaceuticals (Basel, Switzerland) · 2026Review
- Insulin receptorNature communications · 2026Article
- Capivasertib-Induced Diabetes Successfully Managed With Insulin-Independent Glucose-Lowering Agents: A Case Report.Cureus · 2026Article
- Isoleucine and valine regulate the BCAA antagonism by influencing insulin function in broiler chickens.Journal of animal science and biotechnology · 2026Article
- Evaluation of the CHG index for identifying metabolic dysfunction associated steatotic liver disease: evidence from two independent Asian non-obese populations.Frontiers in nutrition · 2026Article
- Association of Metabolic Syndrome and Cholelithiasis: Understanding the Underlying Mechanism for Better Treatment.Mini reviews in medicinal chemistry · 2026Review
- Lipid profile and non-alcoholic fatty liver disease detected by ultrasonography: is systemic inflammation a necessary mediator?Annals of medicine · 2025Article
- Fructose and follistatin potentiate acute MASLD during complete hepatic insulin resistance.Nature communications · 2025Article
- Evaluation of Aqueous Maceration and Ultrasound-Assisted Extracts ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications.Diabetes & metabolism journal · 2025Review
- Obesity-associated macrophages dictate adipose stem cell ferroptosis and visceral fat dysfunction by propagating mitochondrial fragmentation.Nature communications · 2025Article
- NSUN2 knockdown ameliorates hepatic glucose and lipid metabolism disorders in type 2 diabetes mellitus through the Inhibition of ACSL6 m5C methylation.Lipids in health and disease · 2025Article
- Metabolic dysfunction-associated steatotic liver disease in people with HIV.Current opinion in HIV and AIDS · 2025Review
- Spatial regulation of glucose and lipid metabolism by hepatic insulin signaling.Cell metabolism · 2025Article
- Hepatic Glucose Uptake During Euglycemic Hyperinsulinemia Associates With Glycemia During Oral Glucose Tolerance Test.Journal of the Endocrine Society · 2025Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance--wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-(13)C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently. These experiments were performed in normal rats, high fat-fed insulin-resistant rats, and insulin receptor 2'-O-methoxyethyl chimeric antisense oligonucleotide-treated rats. Rates of fatty acid esterification into hepatic triglyceride were found to be dependent on plasma fatty acid infusion rates, independent of changes in plasma insulin concentrations and independent of hepatocellular insulin signaling. Taken together, these results obviate a paradox of selective insulin resistance, because the major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action.
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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.