ArticleThe Journal of biological chemistry2010
Liver X receptor agonists augment human islet function through activation of anaplerotic pathways and glycerolipid/free fatty acid cycling.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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
23 citing papers in PubMed, 45 citations in OpenAlex.
- Human islet amyloid polypeptide aggregation upregulates the mitochondrial cholesterol transport protein StAR and induces mitochondrial dysfunction in beta cells.Diabetologia · 2026Article
- From Nuclear Receptor Regulation to Spleen Activating and Accumulation Resolving Therapy: A Review of Traditional Chinese Medicine Against Diabetes and Inflammation.International journal of molecular sciences · 2025Review
- Nuclear Receptors in Energy Metabolism.Advances in experimental medicine and biology · 2022Article
- Functional characterization of T2D-associated SNP effects on baseline and ER stress-responsive β cell transcriptional activation.Nature communications · 2021Article
- Article
- Genetic obesity increases pancreatic expression of mitochondrial proteins which regulate cholesterol efflux in BRIN-BD11 insulinoma cells.Bioscience reports · 2019Article
- Endoplasmic reticulum stress alters ryanodine receptor function in the murine pancreatic β cell.The Journal of biological chemistry · 2019Article
- Article
- Apolipoprotein E is a pancreatic extracellular factor that maintains mature β-cell gene expression.PloS one · 2018Article
- Liver X receptors link lipid metabolism and inflammation.FEBS letters · 2017Review
- Nitric oxide stress and activation of AMP-activated protein kinase impair β-cell sarcoendoplasmic reticulum calcium ATPase 2b activity and protein stability.Cell death & disease · 2015Article
- Cold Exposure Improves the Anti-diabetic Effect of T0901317 in Streptozotocin-Induced Diabetic Mice.The AAPS journal · 2015Article
- Pancreatic and duodenal homeobox protein 1 (Pdx-1) maintains endoplasmic reticulum calcium levels through transcriptional regulation of sarco-endoplasmic reticulum calcium ATPase 2b (SERCA2b) in the islet β cell.The Journal of biological chemistry · 2014Article
- Human adipose-derived stromal/stem cells protect against STZ-induced hyperglycemia: analysis of hASC-derived paracrine effectors.Stem cells (Dayton, Ohio) · 2014Article
- Coordinated Actions of FXR and LXR in Metabolism: From Pathogenesis to Pharmacological Targets for Type 2 Diabetes.International journal of endocrinology · 2014Review
- Rosiglitazone promotes PPARγ-dependent and -independent alterations in gene expression in mouse islets.Endocrinology · 2012Article
- Article
- RXR Partial Agonist CBt-PMN Exerts Therapeutic Effects on Type 2 Diabetes without the Side Effects of RXR Full Agonists.ACS medicinal chemistry letters · 2012Article
- Lipid raft: A floating island of death or survival.Toxicology and applied pharmacology · 2012Review
- Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR.Nature reviews. Molecular cell biology · 2012Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Recent studies in rodent models suggest that liver X receptors (LXRs) may play an important role in the maintenance of glucose homeostasis and islet function. To date, however, no studies have comprehensively examined the role of LXRs in human islet biology. Human islets were isolated from non-diabetic donors and incubated in the presence or absence of two synthetic LXR agonists, TO-901317 and GW3965, under conditions of low and high glucose. LXR agonist treatment enhanced both basal and stimulated insulin secretion, which corresponded to an increase in the expression of genes involved in anaplerosis and reverse cholesterol transport. Furthermore, enzyme activity of pyruvate carboxylase, a key regulator of pyruvate cycling and anaplerotic flux, was also increased. Whereas LXR agonist treatment up-regulated known downstream targets involved in lipogenesis, we observed no increase in the accumulation of intra-islet triglyceride at the dose of agonist used in our study. Moreover, LXR activation increased expression of the genes encoding hormone-sensitive lipase and adipose triglyceride lipase, two enzymes involved in lipolysis and glycerolipid/free fatty acid cycling. Chronically, insulin gene expression was increased after treatment with TO-901317, and this was accompanied by increased Pdx-1 nuclear protein levels and enhanced Pdx-1 binding to the insulin promoter. In conclusion, our data suggest that LXR agonists have a direct effect on the islet to augment insulin secretion and expression, actions that should be considered either as therapeutic or unintended side effects, as these agents are developed for clinical use.
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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.