ArticleThe Journal of biological chemistry2014
Chronic high glucose and pyruvate levels differentially affect mitochondrial bioenergetics and fuel-stimulated insulin secretion from clonal INS-1 832/13 cells.
Article in The Journal of biological chemistry, 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
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
23 citing papers in PubMed, 39 citations in OpenAlex.
- Impaired glucose tolerance and mild diabetes induce β-cell dysfunction in mice.Nature communications · 2026Article
- Contrasting Effects of Chronic Glucokinase Activation and Inhibition on Pancreatic Beta-Cell Function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Comparative Analysis of Orthosteric and Allosteric GLP-1R Agonists' Effects on Insulin Secretion from Healthy, Diabetic, and Recovered INS-1E Pancreatic Beta Cells.International journal of molecular sciences · 2024Article
- Review
- Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells.Nature communications · 2022Article
- Review
- Mitochondrial Carriers Regulating Insulin Secretion Profiled in Human Islets upon Metabolic Stress.Biomolecules · 2020Article
- Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases.Cells · 2019Review
- Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells.Nature communications · 2019Article
- Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients.European journal of applied physiology · 2019Article
- Metabolic activation-driven mitochondrial hyperpolarization predicts insulin secretion in human pancreatic beta-cells.Biochimica et biophysica acta. Bioenergetics · 2018Article
- Inositol hexakisphosphate kinase 1 is a metabolic sensor in pancreatic β-cells.Cellular signalling · 2018Article
- The impact of IUGR on pancreatic islet development and β-cell function.The Journal of endocrinology · 2017Review
- Transcribing β-cell mitochondria in health and disease.Molecular metabolism · 2017Review
- Mitochondrial transcription factor B2 is essential for mitochondrial and cellular function in pancreatic β-cells.Molecular metabolism · 2017Article
- Article
- Dysregulated mitochondrial and chloroplast bioenergetics from a translational medical perspective (Review).International journal of molecular medicine · 2016Review
- Metabolomics applied to the pancreatic islet.Archives of biochemistry and biophysics · 2016Review
- Mitochondria, Chloroplasts in Animal and Plant Cells: Significance of Conformational Matching.Medical science monitor : international medical journal of experimental and clinical research · 2015Review
- Chronic Exposure to Excess Nutrients Left-shifts the Concentration Dependence of Glucose-stimulated Insulin Secretion in Pancreatic β-Cells.The Journal of biological chemistry · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucotoxicity in pancreatic β-cells is a well established pathogenetic process in type 2 diabetes. It has been suggested that metabolism-derived reactive oxygen species perturb the β-cell transcriptional machinery. Less is known about altered mitochondrial function in this condition. We used INS-1 832/13 cells cultured for 48 h in 2.8 mm glucose (low-G), 16.7 mm glucose (high-G), or 2.8 mm glucose plus 13.9 mm pyruvate (high-P) to identify metabolic perturbations. High-G cells showed decreased responsiveness, relative to low-G cells, with respect to mitochondrial membrane hyperpolarization, plasma membrane depolarization, and insulin secretion, when stimulated acutely with 16.7 mm glucose or 10 mm pyruvate. In contrast, high-P cells were functionally unimpaired, eliminating chronic provision of saturating mitochondrial substrate as a cause of glucotoxicity. Although cellular insulin content was depleted in high-G cells, relative to low-G and high-P cells, cellular functions were largely recovered following a further 24-h culture in low-G medium. After 2 h at 2.8 mm glucose, high-G cells did not retain increased levels of glycolytic or TCA cycle intermediates but nevertheless displayed increased glycolysis, increased respiration, and an increased mitochondrial proton leak relative to low-G and high-P cells. This notwithstanding, titration of low-G cells with low protonophore concentrations, monitoring respiration and insulin secretion in parallel, showed that the perturbed insulin secretion of high-G cells could not be accounted for by increased proton leak. The present study supports the idea that glucose-induced disturbances of stimulus-secretion coupling by extramitochondrial metabolism upstream of pyruvate, rather than exhaustion from metabolic overload, underlie glucotoxicity in insulin-producing cells.
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.