ArticleDiabetes2020
Nutrient-Induced Metabolic Stress, Adaptation, Detoxification, and Toxicity in the Pancreatic β-Cell.
Article in Diabetes, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 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
99 citing papers in PubMed, 144 citations in OpenAlex.
- Effects of short-term tofogliflozin treatment on the insulin secretory capacity of people with type 2 diabetes: A randomized controlled trial, the TOP-ELM study.Journal of diabetes investigation · 2026Trial
- β Cell function and plasma insulin clearance in people with obesity and different glycemic status.The Journal of clinical investigation · 2022Trial
- Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.Life science alliance · 2026Article
- Exercise preserves β-cell function in type 2 diabetes by reshaping intra-islet macrophage-β-cell crosstalk.Life metabolism · 2026Article
- Correspondence: Effects of short-term tofogliflozin treatment on insulin secretory capacity in type 2 diabetes: Insights and future directions.Journal of diabetes investigation · 2026Article
- Gut microbiota translocation contributes to early islet apoptosis in streptozotocin-induced diabetes.mSystems · 2026Article
- A dish-to-biobank framework links β-cell nutrient-stress programs to genetic and dietary risk for Type 2 Diabetes.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial dysfunction-driven inflammation and β-Cell apoptosis in type 2 diabetes mellitus: mechanistic insights and therapeutic implications.Molecular biology reports · 2026Review
- ERp46 mitigates lipotoxic ER stress to preserve GLUT2 expression and insulin secretion in β-cells.Biomedical reports · 2026Article
- Atherogenic index of plasma is associated with poor prognosis in diabetic patients with acute kidney injury.Frontiers in endocrinology · 2026Article
- Copper-molybdenum interactions in ruminant nutrition and reproductive physiology: mechanistic insights into growth, digestibility, and follicular development.Frontiers in veterinary science · 2026Review
- Review
- Insulin Resistance at the Crossroads of Metabolic Inflammation, Cardiovascular Disease, Organ Failure and Cancer.Biomolecules · 2025Review
- GLP-1R associates with VAPB and SPHKAP at ERMCSs to regulate β-cell mitochondrial remodelling and function.Nature communications · 2025Article
- Ingested PET microplastics alter the metabolomic profile of the porcine pancreas.Scientific reports · 2025Article
- Genome-wide CRISPR Screen Identifies Sec31A as a Key Regulator of Alpha Cell Survival.Nature communications · 2025Article
- The role of the beta cell in type 2 diabetes: new findings from the last 5 years.Diabetologia · 2025Review
- Molecular Mechanisms of Human Pancreatic Islet Dysfunction Under Overnutrition Metabolic Stress.Diabetes · 2025Article
- Dynamic Ca2+-Dependent Transcription Links Metabolic Stress to Impaired β-Cell Identity.Diabetes · 2025Article
- Plant-Based Potential in Diabetes Management: In Vitro Antioxidant, Wound-Healing, and Enzyme Inhibitory Activities of Southern Algarve Species.Molecules (Basel, Switzerland) · 2025Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Comment on
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Paraphrasing the Swiss physician and father of toxicology Paracelsus (1493-1541) on chemical agents used as therapeutics, "the dose makes the poison," it is now realized that this aptly applies to the calorigenic nutrients. The case here is the pancreatic islet β-cell presented with excessive levels of nutrients such as glucose, lipids, and amino acids. The short-term effects these nutrients exert on the β-cell are enhanced insulin biosynthesis and secretion and changes in glucose sensitivity. However, chronic fuel surfeit triggers additional compensatory and adaptive mechanisms by β-cells to cope with the increased insulin demand or to protect itself. When these mechanisms fail, toxicity due to the nutrient surplus ensues, leading to β-cell dysfunction, dedifferentiation, and apoptosis. The terms glucotoxicity, lipotoxicity, and glucolipotoxicity have been widely used, but there is some confusion as to what they mean precisely and which is most appropriate for a given situation. Here we address the gluco-, lipo-, and glucolipo-toxicities in β-cells by assessing the evidence both for and against each of them. We also discuss potential mechanisms and defend the view that many of the identified "toxic" effects of nutrient excess, which may also include amino acids, are in fact beneficial adaptive processes. In addition, candidate fuel-excess detoxification pathways are evaluated. Finally, we propose that a more general term should be used for the in vivo situation of overweight-associated type 2 diabetes reflecting both the adaptive and toxic processes to mixed calorigenic nutrients excess: "nutrient-induced metabolic stress" or, in brief, "nutri-stress."
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.