ArticleThe Journal of clinical investigation2009
Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 178 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.
The Role of Gut Hormones and Hepcidin in Type 2 Diabetes Mellitus
Defining Adipose Tissue Lipid Deposition in Normal Weight Individuals With a Genetic Predisposition to Insulin Resistance
Who cites it
178 citing papers in PubMed, 1 synthesis or guideline pooled it, 334 citations in OpenAlex.
- Berberine and health outcomes: an overview of systematic reviews.BMC complementary medicine and therapies · 2025Pooled it
- Efficacy and Safety of Obeticholic Acid for Treating Hepatic Steatosis in Patients With Familial Partial Lipodystrophy.The Journal of clinical endocrinology and metabolism · 2025Trial
- Trial
- Free fatty acid processing diverges in human pathologic insulin resistance conditions.The Journal of clinical investigation · 2020Trial
- Intrahepatic Fat and Postprandial Glycemia Increase After Consumption of a Diet Enriched in Saturated Fat Compared With Free Sugars.Diabetes care · 2020Trial
- Hepatic de novo lipogenesis is suppressed and fat oxidation is increased by omega-3 fatty acids at the expense of glucose metabolism.BMJ open diabetes research & care · 2020Trial
- Thyroid Hormone Effects on Glucose Disposal in Patients With Insulin Receptor Mutations.The Journal of clinical endocrinology and metabolism · 2020Trial
- Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study.Diabetes care · 2018Trial
- Sex Differences in HepaticNutrients · 2018Trial
- Metreleptin improves blood glucose in patients with insulin receptor mutations.The Journal of clinical endocrinology and metabolism · 2013Trial
- The liver diseases of lipodystrophy: the long-term effect of leptin treatment.Journal of hepatology · 2013Trial
- The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans.The Journal of clinical investigation · 2012Trial
- Insulin resistance in the 21st century: new takes on an old problem-2025 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2026Review
- Functional genomic analysis reveals HAVCR1 as the key regulator of 5q33.3 locus linked to hyperlipidemia.HGG advances · 2026Article
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Lipodystrophy: an uncommon cause of insulin resistance and young-onset diabetes.JCEM case reports · 2026Article
- Stable Isotopes for the Study of Energy Nutrient Metabolic Pathways in Relation to Health and Disease.Metabolites · 2026Review
- Maturity Onset Diabetes of the Young (MODY): French National Diagnosis and Care Protocol (PNDS, Protocole National de Diagnostic et de Soins).Orphanet journal of rare diseases · 2026Review
- Serum Proteomics of Insulin Resistance Disorders Distinguish MASLD From Lipodystrophy and Insulin Receptor Defects.The Journal of clinical endocrinology and metabolism · 2026Article
- Familial Generalized and Partial Lipodystrophies Due to Rare Biallelic Variants inInternational journal of molecular sciences · 2026Article
118 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and low HDL cholesterol levels and is frequently accompanied by hepatic steatosis. Increased hepatic lipogenesis contributes to both of these problems. Because insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis in both obese and lipodystrophic insulin-resistant mice, it has been proposed that a selective postreceptor defect in hepatic insulin action is central to the pathogenesis of fatty liver and hypertriglyceridemia in these mice. Here we show that humans with generalized insulin resistance caused by either mutations in the insulin receptor gene or inhibitory antibodies specific for the insulin receptor uniformly exhibited low serum TG and normal HDL cholesterol levels. This was due at least in part to surprisingly low rates of de novo lipogenesis and was associated with low liver fat content and the production of TG-depleted VLDL cholesterol particles. In contrast, humans with a selective postreceptor defect in AKT2 manifest increased lipogenesis, elevated liver fat content, TG-enriched VLDL, hypertriglyceridemia, and low HDL cholesterol levels. People with lipodystrophy, a disorder characterized by particularly severe insulin resistance and dyslipidemia, demonstrated similar abnormalities. Collectively these data from humans with molecularly characterized forms of insulin resistance suggest that partial postreceptor hepatic insulin resistance is a key element in the development of metabolic dyslipidemia and hepatic steatosis.
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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.