ReviewMetabolism: clinical and experimental2021
The β-cell glucose toxicity hypothesis: Attractive but difficult to prove.
Review in Metabolism: clinical and experimental, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed.
- Models of hyperglycaemia in diabetes mellitus and its complications.Nature reviews. Endocrinology · 2026Review
- Is high insulin protective or detrimental? Mathematical modeling reveals the base of the iceberg.American journal of physiology. Endocrinology and metabolism · 2026Article
- Combined immune checkpoint inhibitor-induced type 1 diabetes: a rare but serious endocrinopathy.JCEM case reports · 2026Article
- Early insulin averts hyperglycemic crisis in slow-onset durvalumab-induced checkpoint inhibitor-associated autoimmune diabetes mellitus.Journal of rural medicine : JRM · 2025Article
- Insulin Secretion and Insulin Sensitivity Change in Different Stages of Adult-Onset Type 1 Diabetes: A Cross-Sectional Study.Journal of clinical medicine · 2025Article
- Retrospective derivation of a causal pathway for diabetic ketoacidosis in adult patients with type 2 diabetes mellitus.BMJ open diabetes research & care · 2024Article
- Review
- Short-term recovery of insulin secretion in response to a meal is associated with future glycemic control in type 2 diabetes patients.Journal of diabetes investigation · 2024Article
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- Quantifying beta cell function in the preclinical stages of type 1 diabetes.Diabetologia · 2023Review
- β Cell Stress and Endocrine Function During T1D: What Is Next to Discover?Endocrinology · 2023Article
- Human Pancreatic Islets React to Glucolipotoxicity by Secreting Pyruvate and Citrate.Nutrients · 2023Article
- Article
- Induction of remission in diabetes by lowering blood glucose.Frontiers in endocrinology · 2023Article
- Comprehensive Search for GPCR Compounds which Can Enhance MafA and/or PDX-1 Expression Levels Using a Small Molecule Compound Library.Journal of diabetes research · 2023Article
- Hepatic Steatosis and High-Normal Fasting Glucose as Risk Factors for Incident Prediabetes.Journal of the Endocrine Society · 2022Article
- Review
- High Prevalence of Abnormal Carcinoembryonic Antigen in Diabetic Inpatients with Poor Glycemic Control.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- Alpha-to-beta cell trans-differentiation for treatment of diabetes.Biochemical Society transactions · 2021Review
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
β cells in the hyperglycemic environment of diabetes have marked changes in phenotype and function that are largely reversible if glucose levels can be returned to normal. A leading hypothesis is that these changes are caused by the elevated glucose levels leading to the concept of glucose toxicity. Support for the glucose toxicity hypothesis is largely circumstantial, but little progress has been made in defining the responsible mechanisms. Then questions emerge that are difficult to answer. In the very earliest stages of diabetes development, there is a dramatic loss of glucose-induced first-phase insulin release (FPIR) with only trivial elevations of blood glucose levels. A related question is how impaired insulin action on target tissues such as liver, muscle and fat can cause increased insulin secretion. The existence of a sophisticated feedback mechanism between insulin secretion and insulin action on peripheral tissues driven by glucose has been postulated, but it has been difficult to measure increases in blood glucose levels that might have been expected. These complexities force us to challenge the simplicity of the glucose toxicity hypothesis and feedback mechanisms. It may turn out that glucose is somehow driving all of these changes, but we must develop new questions and experimental approaches to test the hypothesis.
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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 OpenQuestion graph.