ArticleThe Journal of biological chemistry2013
Direct measurements of oscillatory glycolysis in pancreatic islet β-cells using novel fluorescence resonance energy transfer (FRET) biosensors for pyruvate kinase M2 activity.
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 54 papers.
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Who cites it
54 citing papers in PubMed, 86 citations in OpenAlex.
- Trial
- ECM Proteins Nidogen-1 and Decorin Restore Functionality of Human Islets of Langerhans upon Hypoxic Conditions.Advanced healthcare materials · 2025Article
- Review
- Article
- Deconstructing the integrated oscillator model for pancreatic β-cells.Mathematical biosciences · 2023Article
- Article
- Dynamic fluctuations in a bacterial metabolic network.Nature communications · 2023Article
- The Dynamics of Calcium Signaling in Beta Cells-A Discussion on the Comparison of Experimental and Modelling Data.International journal of molecular sciences · 2023Article
- Characteristic stacked structures and luminescent properties of dinuclear lanthanide complexes with pyrene units.Frontiers in chemistry · 2023Article
- ROCK1 regulates insulin secretion from β-cells.Molecular metabolism · 2022Article
- Article
- Monitoring glycolytic dynamics in single cells using a fluorescent biosensor for fructose 1,6-bisphosphate.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Metabolic cycles and signals for insulin secretion.Cell metabolism · 2022Review
- Pulsatile Basal Insulin Secretion Is Driven by Glycolytic Oscillations.Physiology (Bethesda, Md.) · 2022Review
- Slow oscillations persist in pancreatic beta cells lacking phosphofructokinase M.Biophysical journal · 2022Article
- From Isles of Königsberg to Islets of Langerhans: Examining the Function of the Endocrine Pancreas Through Network Science.Frontiers in endocrinology · 2022Review
- Beta-Cell Ion Channels and Their Role in Regulating Insulin Secretion.Comprehensive Physiology · 2021Review
- The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on [Formula: see text] dynamics.Scientific reports · 2021Article
- Intercellular communication induces glycolytic synchronization waves between individually oscillating cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Symbiosis of Electrical and Metabolic Oscillations in Pancreatic β-Cells.Frontiers in physiology · 2021Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pulses of insulin released from pancreatic β-cells maintain blood glucose in a narrow range, although the source of these pulses is unclear. We and others have proposed that positive feedback mediated by the glycolytic enzyme phosphofructokinase-1 (PFK1) enables β-cells to generate metabolic oscillations via autocatalytic activation by its product fructose 1,6-bisphosphate (FBP). Although much indirect evidence has accumulated in favor of this hypothesis, a direct measurement of oscillating glycolytic intermediates has been lacking. To probe glycolysis directly, we engineered a family of inter- and intramolecular FRET biosensors based on the glycolytic enzyme pyruvate kinase M2 (PKAR; pyruvate kinase activity reporter), which multimerizes and is activated upon binding FBP. When introduced into Min6 β-cells, PKAR FRET efficiency increased rapidly in response to glucose. Importantly, however, metabolites entering downstream of PFK1 (glyceraldehyde, pyruvate, and ketoisocaproate) failed to activate PKAR, consistent with sensor activation by FBP; the dependence of PKAR on FBP was further confirmed using purified sensor in vitro. Using a novel imaging modality for monitoring mitochondrial flavin fluorescence in mouse islets, we show that slow oscillations in mitochondrial redox potential stimulated by 10 mm glucose are in phase with glycolytic efflux through PKM2, measured simultaneously from neighboring islet β-cells expressing PKAR. These results indicate that PKM2 activity in β-cells is oscillatory and are consistent with pulsatile PFK1 being the mediator of slow glycolytic oscillations.
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