ReviewDiabetes2024
Glucose Regulation of β-Cell KATP Channels: It Is Time for a New Model!
Review in Diabetes, 2024. 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.
- Effects of Dorzagliatin, a Glucokinase Activator, on α- and β-Cell Function in Individuals With Impaired and Normal Glucose Tolerance.Diabetes · 2025Trial
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Pharmaceutical agents targeting KThe journal of physiological sciences : JPS · 2026Article
- Compartmentalized Nutrient and Hormone Sensing in β-Cells: the Role of Primary Cilia.Physiology (Bethesda, Md.) · 2026Review
- Compartmentalized glycolysis powers ATP production in primary cilia and engages mitochondria via the phosphoenolpyruvate cycle.bioRxiv : the preprint server for biology · 2026Article
- Article
- Therapeutic Trends in Diabetes Management: A Review on Oral Hypoglycemic Agents (OHAs) Utilization in Tertiary Care.Cardiovascular & hematological disorders drug targets · 2026Review
- Restoration of PKM1 improves functional maturation of human stem-cell derived-β cell by regulating PEP metabolism.Nature communications · 2025Article
- The effects of free fatty acid-free bovine serum albumin and palmitate on pancreatic β-cell function.Islets · 2025Article
- Nonsteroidal Anti-Inflammatory Drugs as Modulators of Cation Channels: Fenamates Repurposing in Channelopathies.ChemMedChem · 2025Review
- The Amount of Releasable Insulin Depends on Continuous Oxidative Phosphorylation.Function (Oxford, England) · 2025Article
- Calorie Restriction modulates beta cell IPbioRxiv : the preprint server for biology · 2025Article
- An INS-1 832/13 𝛽-Cell Proteome Highlights the Rapid Regulation of Fatty Acid Biosynthesis in Glucose-Stimulated Insulin Secretion.Proteomics · 2025Article
- The RhoGDIβ-Rac1-CARD9 Signaling Module Mediates Islet β-Cell Dysfunction Under Chronic Hyperglycemia.Cells · 2025Review
- Bayliss-Starling Prize Lecture: KThe Journal of physiology · 2025Article
- Amino acid sensing by the α-cell mitochondrial phosphoenolpyruvate cycle regulates intracellular CabioRxiv : the preprint server for biology · 2025Article
- Pyruvate kinase modulates the link between β-cell fructose metabolism and insulin secretion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Stimulus-Secretion Coupling Mechanisms of Glucose-Induced Insulin Secretion: Biochemical Discrepancies Among the Canonical, ADP Privation, and GABA-Shunt Models.International journal of molecular sciences · 2025Review
- The Synergistic Impact of Glycolysis, Mitochondrial OxPhos, and PEP Cycling on ATP Production in Beta Cells.International journal of molecular sciences · 2025Article
- Biphasic glucose-stimulated insulin secretion over decades: a journey from measurements and modeling to mechanistic insights.Life metabolism · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
An agreed-upon consensus model of glucose-stimulated insulin secretion from healthy β-cells is essential for understanding diabetes pathophysiology. Since the discovery of the KATP channel in 1984, an oxidative phosphorylation (OxPhos)-driven rise in ATP has been assumed to close KATP channels to initiate insulin secretion. This model lacks any evidence, genetic or otherwise, that mitochondria possess the bioenergetics to raise the ATP/ADP ratio to the triggering threshold, and conflicts with genetic evidence demonstrating that OxPhos is dispensable for insulin secretion. It also conflates the stoichiometric yield of OxPhos with thermodynamics, and overestimates OxPhos by failing to account for established features of β-cell metabolism, such as leak, anaplerosis, cataplerosis, and NADPH production that subtract from the efficiency of mitochondrial ATP production. We have proposed an alternative model, based on the spatial and bioenergetic specializations of β-cell metabolism, in which glycolysis initiates insulin secretion. The evidence for this model includes that 1) glycolysis has high control strength over insulin secretion; 2) glycolysis is active at the correct time to explain KATP channel closure; 3) plasma membrane-associated glycolytic enzymes control KATP channels; 4) pyruvate kinase has favorable bioenergetics, relative to OxPhos, for raising ATP/ADP; and 5) OxPhos stalls before membrane depolarization and increases after. Although several key experiments remain to evaluate this model, the 1984 model is based purely on circumstantial evidence and must be rescued by causal, mechanistic experiments if it is to endure.
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What Socratic 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 Socratic graph.