ArticleThe Journal of biological chemistry2013
Coordinate changes in histone modifications, mRNA levels, and metabolite profiles in clonal INS-1 832/13 β-cells accompany functional adaptations to lipotoxicity.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 71 citations in OpenAlex.
- RNASET2 degrades mRNAs that protect against lipotoxicity.Molecular metabolism · 2026Article
- Epigenetic regulation in a high-sugar environment (Review).International journal of molecular medicine · 2026Review
- Genetics and epigenetics of diabetes and its complications in India.Human genetics · 2024Review
- Current insights into genome-based personalized nutrition technology: a patent review.Frontiers in nutrition · 2024Review
- Circulating triglycerides are associated with human adipose tissue DNA methylation of genes linked to metabolic disease.Human molecular genetics · 2023Article
- A pathway model of glucose-stimulated insulin secretion in the pancreaticFrontiers in endocrinology · 2023Article
- The impact of macronutrient composition on metabolic regulation: An Islet-Centric view.Acta physiologica (Oxford, England) · 2022Article
- Kinetic and data-driven modeling of pancreatic β-cell central carbon metabolism and insulin secretion.PLoS computational biology · 2022Article
- Epigenetics of type 2 diabetes mellitus and weight change - a tool for precision medicine?Nature reviews. Endocrinology · 2022Review
- A High-Cholesterol Diet Increases Toll-like Receptors and Other Harmful Factors in the Rabbit Myocardium: The Beneficial Effect of Statins.Current issues in molecular biology · 2021Article
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Molecular Mechanisms of Nutrient-Mediated Regulation of MicroRNAs in Pancreatic β-cells.Frontiers in endocrinology · 2021Review
- Enhancer of Zeste Homolog 2 (EZH2) Mediates Glucolipotoxicity-Induced Apoptosis in β-Cells.International journal of molecular sciences · 2020Article
- Combined transcriptome and proteome profiling of the pancreatic β-cell response to palmitate unveils key pathways of β-cell lipotoxicity.BMC genomics · 2020Article
- Oleic acid influences the adipogenesis of 3T3-L1 cells via DNA Methylation and may predispose to obesity and obesity-related disorders.Lipids in health and disease · 2019Article
- Dietary Fat and the Genetic Risk of Type 2 Diabetes.Current diabetes reports · 2019Review
- Physiological phenotyping of mammalian cell lines by enzymatic activity fingerprinting of key carbohydrate metabolic enzymes: a pilot and feasibility study.BMC research notes · 2019Article
- ATAC-seq reveals alterations in open chromatin in pancreatic islets from subjects with type 2 diabetes.Scientific reports · 2019Article
- Epigenetics in Human Obesity and Type 2 Diabetes.Cell metabolism · 2019Review
- Regulation of cAMP accumulation and activity by distinct phosphodiesterase subtypes in INS-1 cells and human pancreatic β-cells.PloS one · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipotoxicity is a presumed pathogenetic process whereby elevated circulating and stored lipids in type 2 diabetes cause pancreatic β-cell failure. To resolve the underlying molecular mechanisms, we exposed clonal INS-1 832/13 β-cells to palmitate for 48 h. We observed elevated basal insulin secretion but impaired glucose-stimulated insulin secretion in palmitate-exposed cells. Glucose utilization was unchanged, palmitate oxidation was increased, and oxygen consumption was impaired. Halting exposure of the clonal INS-1 832/13 β-cells to palmitate largely recovered all of the lipid-induced functional changes. Metabolite profiling revealed profound but reversible increases in cellular lipids. Glucose-induced increases in tricarboxylic acid cycle intermediates were attenuated by exposure to palmitate. Analysis of gene expression by microarray showed increased expression of 982 genes and decreased expression of 1032 genes after exposure to palmitate. Increases were seen in pathways for steroid biosynthesis, cell cycle, fatty acid metabolism, DNA replication, and biosynthesis of unsaturated fatty acids; decreases occurred in the aminoacyl-tRNA synthesis pathway. The activity of histone-modifying enzymes and histone modifications of differentially expressed genes were reversibly altered upon exposure to palmitate. Thus, Insig1, Lss, Peci, Idi1, Hmgcs1, and Casr were subject to epigenetic regulation. Our analyses demonstrate that coordinate changes in histone modifications, mRNA levels, and metabolite profiles accompanied functional adaptations of clonal β-cells to lipotoxicity. It is highly likely that these changes are pathogenetic, accounting for loss of glucose responsiveness and perturbed insulin secretion.
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.