ArticleMolecular metabolism2020
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.
Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
36 citing papers in PubMed, 3 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- The Effects of SGLT2 Inhibitors on Muscle Health in Older Adults: A Systematic Review and Meta-Analysis.Pharmacology research & perspectives · 2026Pooled it
- iCatCare 2025 consensus guidelines on the diagnosis and management of diabetes mellitus in cats.Journal of feline medicine and surgery · 2025Guideline
- The safety of sotagliflozin in the therapy of diabetes mellitus type 1 and type 2: A meta-analysis of randomized trials.Frontiers in endocrinology · 2022Pooled it
- 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
- Trial
- Empagliflozin inhibits the apoptosis of pancreatic β-cells through amelioration of endoplasmic reticulum (ER) stress.Metabolism open · 2026Article
- Dapagliflozin attenuates hepatic steatosis and induces a fasting-mimicking metabolic state in C57BL/6 mice.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Highly selective SGLT2 inhibitors suppress glucose uptake in alpha-TC1 cells, while glucagon secretion is not affected.Hormones (Athens, Greece) · 2026Article
- Metabolic Reprogramming Coordinates Mannose and Glutamine Metabolism to Maintain Glucose Homeostasis During Glycosuria.bioRxiv : the preprint server for biology · 2026Article
- Pancreatic α-cell sodium-glucose cotransporter 1 (SGLT1) does not appear to contribute to hyperglucagonemia and glucose intolerance in diabetic mice.Endocrine journal · 2026Article
- The SGLT2 Inhibitor Canagliflozin Promotes β-Cell Regeneration and Restores and Stabilises β-Cell Identity in a Polygenic Model of Severe Early-Onset Type 2 Diabetes.Journal of cellular and molecular medicine · 2026Article
- The SGLT2 inhibitor checklist: a comprehensive review of perioperative and acute phase safety management.Frontiers in endocrinology · 2026Review
- Sodium-glucose transporters SGLT1 and SGLT2 in equine renal, hepatic and pancreatic tissue.BMC veterinary research · 2025Article
- Sodium-glucose co-transporter 2 inhibitors: Prospects for canine myxomatous mitral valve disease and finding the "right drug" and the "right dose" for dogs.The Journal of veterinary medical science · 2025Review
- Dehydration-induced AVP stimulates glucagon release and ketogenesis.American journal of physiology. Endocrinology and metabolism · 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
- The novel antidiabetic medications on diabetic retinopathy: relevant molecular mechanisms, advancing diagnostic innovations, and therapeutic implications.Frontiers in medicine · 2025Review
- Glucose-Lowering Agents Developed in the Last Two Decades and Their Perioperative Implications.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Exogenous Ketones in Cardiovascular Disease and Diabetes: From Bench to Bedside.Journal of clinical medicine · 2024Review
- Dapagliflozin mitigates cellular stress and inflammation through PI3K/AKT pathway modulation in cardiomyocytes, aortic endothelial cells, and stem cell-derived β cells.Cardiovascular diabetology · 2024Article
Corrections and comments
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Authors and funding
23 authors at 8 institutions in 6 countries.
Funding
Abstract
objectiveSodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i), or gliflozins, are anti-diabetic drugs that lower glycemia by promoting glucosuria, but they also stimulate endogenous glucose and ketone body production. The likely causes of these metabolic responses are increased blood glucagon levels, and decreased blood insulin levels, but the mechanisms involved are hotly debated. This study verified whether or not SGLT2i affect glucagon and insulin secretion by a direct action on islet cells in three species, using multiple approaches.
methodsWe tested the in vivo effects of two selective SGLT2i (dapagliflozin, empagliflozin) and a SGLT1/2i (sotagliflozin) on various biological parameters (glucosuria, glycemia, glucagonemia, insulinemia) in mice. mRNA expression of SGLT2 and other glucose transporters was assessed in rat, mouse, and human FACS-purified α- and β-cells, and by analysis of two human islet cell transcriptomic datasets. Immunodetection of SGLT2 in pancreatic tissues was performed with a validated antibody. The effects of dapagliflozin, empagliflozin, and sotagliflozin on glucagon and insulin secretion were assessed using isolated rat, mouse and human islets and the in situ perfused mouse pancreas. Finally, we tested the long-term effect of SGLT2i on glucagon gene expression.
resultsSGLT2 inhibition in mice increased the plasma glucagon/insulin ratio in the fasted state, an effect correlated with a decline in glycemia. Gene expression analyses and immunodetections showed no SGLT2 mRNA or protein expression in rodent and human islet cells, but moderate SGLT1 mRNA expression in human α-cells. However, functional experiments on rat, mouse, and human (29 donors) islets and the in situ perfused mouse pancreas did not identify any direct effect of dapagliflozin, empagliflozin or sotagliflozin on glucagon and insulin secretion. SGLT2i did not affect glucagon gene expression in rat and human islets.
conclusionsThe data indicate that the SGLT2i-induced increase of the plasma glucagon/insulin ratio in vivo does not result from a direct action of the gliflozins on islet cells.
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