ArticleScientific reports2016
Dapagliflozin stimulates glucagon secretion at high glucose: experiments and mathematical simulations of human A-cells.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03965000 (Human SLC5A2 Deficiency and the Glucagon-Incretin Axis), which is not on this map. Cited by 36 papers, 2 of them syntheses that pooled it.
What it found
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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.
Human SLC5A2 Deficiency and the Glucagon-Incretin Axis: A Pilot Study
Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- iCatCare 2025 consensus guidelines on the diagnosis and management of diabetes mellitus in cats.Journal of feline medicine and surgery · 2025Guideline
- Comparative effectiveness and safety of sodium-glucose cotransporter 2 inhibitors vs glucagon-like peptide 1 receptor agonists in elderly patients with type 2 diabetes mellitus: a meta-analysis.Frontiers in endocrinology · 2025Pooled it
- Trial
- Highly selective SGLT2 inhibitors suppress glucose uptake in alpha-TC1 cells, while glucagon secretion is not affected.Hormones (Athens, Greece) · 2026Article
- Ketogenic Diet in Obesity and Diabetes: A Narrative Review.Nutrients · 2026Review
- Sodium-glucose transporters SGLT1 and SGLT2 in equine renal, hepatic and pancreatic tissue.BMC veterinary research · 2025Article
- Dehydration-induced AVP stimulates glucagon release and ketogenesis.American journal of physiology. Endocrinology and metabolism · 2025Article
- Article
- Mathematical Models of the Effect of Glucagon on Glycemia in Individuals With Type 2 Diabetes Treated With Dapagliflozin.Journal of the Endocrine Society · 2024Article
- Genetic and clinical characterization of familial renal glucosuria.Clinical kidney journal · 2024Article
- SGLT2 Inhibition by Dapagliflozin Attenuates Diabetic Ketoacidosis in Mice with Type-1 Diabetes.Cardiovascular drugs and therapy · 2022Article
- Regulation of α-cell glucagon secretion: The role of second messengers.Chronic diseases and translational medicine · 2022Review
- Article
- Sodium, Glucose and Dysregulated Glucagon Secretion: The Potential of Sodium Glucose Transporters.Frontiers in pharmacology · 2022Review
- Mathematical Model of Glucagon Kinetics for the Assessment of Insulin-Mediated Glucagon Inhibition During an Oral Glucose Tolerance Test.Frontiers in endocrinology · 2021Article
- Article
- SGLT2 is not expressed in pancreatic α- and β-cells, and its inhibition does not directly affect glucagon and insulin secretion in rodents and humans.Molecular metabolism · 2020Article
- HNF1α controls glucagon secretion in pancreatic α-cells through modulation of SGLT1.Biochimica et biophysica acta. Molecular basis of disease · 2020Article
- Sodium-glucose cotransporter-2 inhibitors: Understanding the mechanisms for therapeutic promise and persisting risks.The Journal of biological chemistry · 2020Review
- Sodium-glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus.Nature reviews. Endocrinology · 2020 · on this mapReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucagon is one of the main regulators of blood glucose levels and dysfunctional stimulus secretion coupling in pancreatic A-cells is believed to be an important factor during development of diabetes. However, regulation of glucagon secretion is poorly understood. Recently it has been shown that Na(+)/glucose co-transporter (SGLT) inhibitors used for the treatment of diabetes increase glucagon levels in man. Here, we show experimentally that the SGLT2 inhibitor dapagliflozin increases glucagon secretion at high glucose levels both in human and mouse islets, but has little effect at low glucose concentrations. Because glucagon secretion is regulated by electrical activity we developed a mathematical model of A-cell electrical activity based on published data from human A-cells. With operating SGLT2, simulated glucose application leads to cell depolarization and inactivation of the voltage-gated ion channels carrying the action potential, and hence to reduce action potential height. According to our model, inhibition of SGLT2 reduces glucose-induced depolarization via electrical mechanisms. We suggest that blocking SGLTs partly relieves glucose suppression of glucagon secretion by allowing full-scale action potentials to develop. Based on our simulations we propose that SGLT2 is a glucose sensor and actively contributes to regulation of glucagon levels in humans which has clinical implications.
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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.