ArticleThe Journal of clinical investigation2018
Intracellular lipid metabolism impairs β cell compensation during diet-induced obesity.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
27 citing papers in PubMed, 43 citations in OpenAlex.
- Article
- Lipidomic signatures in gestational diabetes mellitus and postpartum type 2 diabetes mellitus: a narrative review of etiologic and predictive implications.EBioMedicine · 2026Review
- Metabolic Adaptation of CD8⁺ T Cells Limits the Efficacy of Fatty Acid Oxidation Inhibition in Type 1 Diabetes.International journal of biological sciences · 2026Article
- Immune activation induced by dysregulated lipid metabolism in the pathogenesis of type 2 diabetes.World journal of diabetes · 2025Review
- Dynamic multi-omics profiling of islet and gut hormonal secretion and peripheral crosstalk in response to various nutrient loads.Cell reports. Medicine · 2025Article
- Oxidative Stress Induced by Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) Dysfunction Aggravates Chronic Inflammation Through the NADAntioxidants (Basel, Switzerland) · 2025Review
- Dioxin-Induced PAI-1 Expression: A Novel Pathway to Pancreatic β-Cell Failure in Type 2 Diabetes.International journal of molecular sciences · 2024Article
- The selective serotonin reuptake inhibitors, sertraline and paroxetine, improve islet beta-cell mass and function in vitro.Diabetes, obesity & metabolism · 2024Article
- Immunometabolic Rewiring: A Tale of Macronutrients and Macrophages.Results and problems in cell differentiation · 2024Review
- Article
- Molecular Changes in Cells of Patients with Type 2 Diabetes Mellitus Depending on Changes in Glycemia Level in the Context of Lifestyle-An Overview of the Latest Scientific Discoveries.Current issues in molecular biology · 2023Review
- Cholesterol Redistribution in Pancreatic β-Cells: A Flexible Path to Regulate Insulin Secretion.Biomolecules · 2023Review
- Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease.Circulation research · 2022Article
- Elevated triglyceride-glucose (TyG) index predicts impaired islet β-cell function: A hospital-based cross-sectional study.Frontiers in endocrinology · 2022Article
- Niacin exacerbates β cell lipotoxicity in diet-induced obesity mice through upregulation of GPR109A and PPARγ2: Inhibition by incretin drugs.Frontiers in endocrinology · 2022Article
- Endothelium-specific depletion of LRP1 improves glucose homeostasis through inducing osteocalcin.Nature communications · 2021Article
- The SARS-CoV-2 SSHHPS Recognized by the Papain-like Protease.ACS infectious diseases · 2021Article
- Article
- Glucocorticoid signaling in pancreatic islets modulates gene regulatory programs and genetic risk of type 2 diabetes.PLoS genetics · 2021Article
- LRP1 regulates food intake and energy balance in GABAergic neurons independently of leptin action.American journal of physiology. Endocrinology and metabolism · 2021Article
Corrections and comments
- Commented on by
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
The compensatory proliferation of insulin-producing β cells is critical to maintaining glucose homeostasis at the early stage of type 2 diabetes. Failure of β cells to proliferate results in hyperglycemia and insulin dependence in patients. To understand the effect of the interplay between β cell compensation and lipid metabolism upon obesity and peripheral insulin resistance, we eliminated LDL receptor-related protein 1 (LRP1), a pleiotropic mediator of cholesterol, insulin, energy metabolism, and other cellular processes, in β cells. Upon high-fat diet exposure, LRP1 ablation significantly impaired insulin secretion and proliferation of β cells. The diminished insulin signaling was partly contributed to by the hypersensitivity to glucose-induced, Ca2+-dependent activation of Erk and the mTORC1 effector p85 S6K1. Surprisingly, in LRP1-deficient islets, lipotoxic sphingolipids were mitigated by improved lipid metabolism, mediated at least in part by the master transcriptional regulator PPARγ2. Acute overexpression of PPARγ2 in β cells impaired insulin signaling and insulin secretion. Elimination of Apbb2, a functional regulator of LRP1 cytoplasmic domain, also impaired β cell function in a similar fashion. In summary, our results uncover the double-edged effects of intracellular lipid metabolism on β cell function and viability in obesity and type 2 diabetes and highlight LRP1 as an essential regulator of these processes.
Indexed as
Identifiers
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.