ArticleJournal of lipid research2014
Hepatic insulin receptor deficiency impairs the SREBP-2 response to feeding and statins.
Article in Journal of lipid research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Trial
- SREBP-2 promotes cancer progression through the mevalonate-Akt pathway in non-small cell lung cancer.Scientific reports · 2025Article
- Rhomboid protease RHBDL4/RHBDD1 cleaves SREBP-1c at endoplasmic reticulum monitoring and regulating fatty acids.PNAS nexus · 2023Article
- Insulin Regulation of Hepatic Lipid Homeostasis.Comprehensive Physiology · 2023Review
- Article
- Latent, sex-specific metabolic health effects in CD-1 mouse offspring exposed to PFOA or HFPO-DA (GenX) during gestation.Emerging contaminants · 2021Article
- RNA-Seq Reveals Different Gene Expression in Liver-Specific Prohibitin 1 Knock-Out Mice.Frontiers in physiology · 2021Article
- Molecular Characterization, Nutritional and Insulin Regulation of Elovl6 in Rainbow Trout (Biomolecules · 2020Article
- Hypoxia-Ischemia Induced Age-Dependent Gene Transcription Effects at Two Development Stages in the Neonate Mouse Brain.Frontiers in molecular neuroscience · 2020Article
- Silencing of SAA1 inhibits palmitate- or high-fat diet induced insulin resistance through suppression of the NF-κB pathway.Molecular medicine (Cambridge, Mass.) · 2019Article
- Article
- Small Heterodimer Partner and Fibroblast Growth Factor 19 Inhibit Expression of NPC1L1 in Mouse Intestine and Cholesterol Absorption.Gastroenterology · 2019Article
- Functional Implications of HMG-CoA Reductase Inhibition on Glucose Metabolism.Korean circulation journal · 2018Review
- FoxO1 Is Required for Most of the Metabolic and Hormonal Perturbations Produced by Hepatic Insulin Receptor Deletion in Male Mice.Endocrinology · 2018Article
- Protective role of endogenous plasmalogens against hepatic steatosis and steatohepatitis in mice.Hepatology (Baltimore, Md.) · 2017Article
- Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Unraveling the Paradox of Selective Insulin Resistance in the Liver: the Brain-Liver Connection.Diabetes · 2016Article
- Insulin Dissociates the Effects of Liver X Receptor on Lipogenesis, Endoplasmic Reticulum Stress, and Inflammation.The Journal of biological chemistry · 2016Article
- Role of Insulin in the Regulation of Proprotein Convertase Subtilisin/Kexin Type 9.Arteriosclerosis, thrombosis, and vascular biology · 2015Article
- Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis.Nature communications · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
The liver plays a central role in metabolism and mediating insulin action. To dissect the effects of insulin on the liver in vivo, we have studied liver insulin receptor knockout (LIRKO) mice. Because LIRKO livers lack insulin receptors, they are unable to respond to insulin. Surprisingly, the most profound derangement observed in LIRKO livers by microarray analysis is a suppression of the cholesterologenic genes. Sterol regulatory element binding protein (SREBP)-2 promotes cholesterologenic gene transcription, and is inhibited by intracellular cholesterol. LIRKO livers show a slight increase in hepatic cholesterol, a 40% decrease in Srebp-2, and a 50-90% decrease in the cholesterologenic genes at the mRNA and protein levels. In control mice, SREBP-2 and cholesterologenic gene expression are suppressed by fasting and restored by refeeding; in LIRKO mice, this response is abolished. Similarly, the ability of statins to induce Srebp-2 and the cholesterologenic genes is lost in LIRKO livers. In contrast, ezetimibe treatment robustly induces Srepb-2 and its targets in LIRKO livers, raising the possibility that insulin may regulate SREBP-2 indirectly, by altering the accumulation or distribution of cholesterol within the hepatocyte. Taken together, these data indicate that cholesterol synthesis is a key target of insulin action in the liver.
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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 Socratic graph.