ArticleThe Journal of biological chemistry2015
Insulin resistance induces posttranslational hepatic sortilin 1 degradation in mice.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Mechanisms and Predisposing Conditions for Statin-Induced New-Onset Type 2 Diabetes Mellitus: A Paradox Relative to Their Pleiotropic Metabolic Effects.Endocrinology, diabetes & metabolism · 2026Review
- The role of sortilin in cardiovascular calcification: mechanisms and therapeutic potential.Frontiers in cardiovascular medicine · 2026Review
- Serum Sortilin Levels as a Biomarker for Metabolic and Hormonal Dysregulation in Polycystic Ovary Syndrome.Journal of personalized medicine · 2025Article
- Sortilin-Mediated Inhibition of TREK1/2 Channels in Primary Sensory Neurons Promotes Prediabetic Neuropathic Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- Regulation of Human Sortilin Alternative Splicing by Glucagon-like Peptide-1 (GLP1) in Adipocytes.International journal of molecular sciences · 2023Article
- Insulin Regulation of Hepatic Lipid Homeostasis.Comprehensive Physiology · 2023Review
- Emerging roles of sortilin in affecting the metabolism of glucose and lipid profiles.Bosnian journal of basic medical sciences · 2022Review
- Sortilin restricts secretion of apolipoprotein B-100 by hepatocytes under stressed but not basal conditions.The Journal of clinical investigation · 2022Article
- Targeting the ASMase/S1P pathway protects from sortilin-evoked vascular damage in hypertension.The Journal of clinical investigation · 2022Article
- The association of plasma sortilin with essential hypertension and subclinical carotid atherosclerosis: A cross-sectional study.Frontiers in cardiovascular medicine · 2022Article
- Oxidized low-density lipoprotein activates extracellular signal-regulated kinase signaling to downregulate sortilin expression in liver sinusoidal endothelial cells.Journal of gastroenterology and hepatology · 2021Article
- The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients.Cancers · 2021Article
- Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study.Cardiovascular diabetology · 2020Article
- Activation of microRNA-378a-3p biogenesis promotes hepatic secretion of VLDL and hyperlipidemia by modulating ApoB100-Sortilin1 axis.Theranostics · 2020Article
- Hepatocyte sortilin 1 knockout and treatment with a sortilin 1 inhibitor reduced plasma cholesterol in Western diet-fed mice.Journal of lipid research · 2019Article
- Sortilin levels are associated with peripheral arterial disease in type 2 diabetic subjects.Cardiovascular diabetology · 2019Article
- Suitability of hepatocyte cell lines HepG2, AML12 and THLE-2 for investigation of insulin signalling and hepatokine gene expression.Open biology · 2018Article
- A mitochondrial proteome profile indicative of type 2 diabetes mellitus in skeletal muscles.Experimental & molecular medicine · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Insulin promotes hepatic apolipoprotein B100 (apoB100) degradation, whereas insulin resistance is a major cause of hepatic apoB100/triglyceride overproduction in type 2 diabetes. The cellular trafficking receptor sortilin 1 (Sort1) was recently identified to transport apoB100 to the lysosome for degradation in the liver and thus regulate plasma cholesterol and triglyceride levels. Genetic variation of SORT1 was strongly associated with cardiovascular disease risk in humans. The major goal of this study is to investigate the effect and molecular mechanism of insulin regulation of Sort1. Results showed that insulin induced Sort1 protein, but not mRNA, in AML12 cells. Treatment of PI3K or AKT inhibitors decreased Sort1 protein, whereas expression of constitutively active AKT induced Sort1 protein in AML12 cells. Consistently, hepatic Sort1 was down-regulated in diabetic mice, which was partially restored after the administration of the insulin sensitizer metformin. LC-MS/MS analysis further revealed that serine phosphorylation of Sort1 protein was required for insulin induction of Sort1 in a casein kinase 2-dependent manner and that inhibition of PI3K signaling or prevention of Sort1 phosphorylation accelerated proteasome-dependent Sort1 degradation. Administration of a PI3K inhibitor to mice decreased hepatic Sort1 protein and increased plasma cholesterol and triglyceride levels. Adenovirus-mediated overexpression of Sort1 in the liver prevented PI3K inhibitor-induced Sort1 down-regulation and decreased plasma triglyceride but had no effect on plasma cholesterol in mice. This study identified Sort1 as a novel target of insulin signaling and suggests that Sort1 may play a role in altered hepatic apoB100 metabolism in insulin-resistant conditions.
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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.