ArticleDiabetes care2021
Hepatic Insulin Resistance Is Not Pathway Selective in Humans With Nonalcoholic Fatty Liver Disease.
Article in Diabetes care, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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.
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Who cites it
59 citing papers in PubMed, 78 citations in OpenAlex.
- Effect of diet macronutrient content on the cardiometabolic response to weight loss: A randomized clinical trial.Cell metabolism · 2026Trial
- Hepatic steatosis in humans is associated with preserved glucagon action on amino acid metabolism.The Journal of clinical investigation · 2026Trial
- Histological improvements following energy restriction and exercise: The role of insulin resistance in resolution of MASH.Journal of hepatology · 2024Trial
- The insulin resistance mosaic: defect, defence or both? A perspective on what insulin resistance means and whether it should be treated.Diabetologia · 2026Article
- Insulin resistance in the 21st century: new takes on an old problem-2025 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2026Review
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- Review
- Substrate supply, compartmentation, and utilization in hepatic de novo lipogenesis.Trends in endocrinology and metabolism: TEM · 2026Review
- Review
- Neuromodulation using Bioelectronics-enabled therapies to combat insulin resistance and its comorbidities.Journal of diabetes and metabolic disorders · 2026Review
- Incretin and Glucagon Signalling in MASLD and MASH: Integrating Metabolic Pathways With Disease Progression.Diabetes, obesity & metabolism · 2026Review
- Altered Molecular Regulation of TUG Is a Central Feature of Insulin-Resistant Human Adipose Tissue.Diabetes · 2026Article
- A microphysiological model of human MASLD reveals paradoxical response to resmetirom.Communications biology · 2026Article
- From the Liver to Heart in Nonalcoholic Fatty Liver Disease: Single-Cell and Serum Evidence for Cytokeratin 18 in Predicting Cardiovascular Risk.Cardiovascular therapeutics · 2026Article
- Role of ChREBP-PPARα-FGF21 Axis in Metabolic Dysfunction of MASLD.International journal of molecular sciences · 2025Article
- Fructose and follistatin potentiate acute MASLD during complete hepatic insulin resistance.Nature communications · 2025Article
- Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways.Clinical science (London, England : 1979) · 2025Review
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
- Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications.Diabetes & metabolism journal · 2025Review
- Skeletal muscle and MASLD: Mechanistic and clinical insights.Hepatology communications · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveBoth glucose and triglyceride production are increased in type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). For decades, the leading hypothesis to explain these paradoxical observations has been selective hepatic insulin resistance wherein insulin drives de novo lipogenesis (DNL) while failing to suppress glucose production. Here, we aimed to test this hypothesis in humans. RESEARCH DESIGN AND
methodsWe recruited obese subjects who met criteria for bariatric surgery with (
resultsCompared with subjects without NAFLD, those with NAFLD demonstrated impaired insulin-mediated suppression of glucose production and attenuated-not increased-glucose-stimulated/high-insulin lipogenesis. Fructose-stimulated/low-insulin lipogenesis was intact. Hepatocellular insulin signaling, assessed for the first time in humans, exhibited a proximal block in insulin-resistant subjects: Signaling was attenuated from the level of the insulin receptor through both glucose and lipogenesis pathways. The carbohydrate-regulated lipogenic transcription factor
conclusionsAcute increases in lipogenesis in humans with NAFLD are not explained by altered molecular regulation of lipogenesis through a paradoxical increase in lipogenic insulin action; rather, increases in lipogenic substrate availability may be the key.
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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.