ArticleMolecular metabolism2019
SGLT1 in pancreatic α cells regulates glucagon secretion in mice, possibly explaining the distinct effects of SGLT2 inhibitors on plasma glucagon levels.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 4 of them syntheses that pooled it.
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Who cites it
64 citing papers in PubMed, 4 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Model-based meta-analysis of HbA1c reduction across SGLT2 inhibitors using dose adjusted by urinary glucose excretion.Scientific reports · 2024Pooled it
- Influence of dipeptidyl peptidase-4 inhibitors on glycemic variability in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.Frontiers in endocrinology · 2022Pooled it
- 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 sodium-glucose cotransporter 2 inhibitors on non-alcoholic fatty liver disease in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.Journal of diabetes investigation · 2020Pooled it
- The sodium-glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes.Scientific reports · 2022Trial
- Improved time in range and postprandial hyperglycemia with canagliflozin in combination with teneligliptin: Secondary analyses of the CALMER study.Journal of diabetes investigation · 2021Trial
- Role of glucagon in metabolic diseases.Journal of diabetes investigation · 2026Review
- Highly selective SGLT2 inhibitors suppress glucose uptake in alpha-TC1 cells, while glucagon secretion is not affected.Hormones (Athens, Greece) · 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
- Sex-specific differences in pancreatic α-cell function.Frontiers in endocrinology · 2026Review
- Effects of canagliflozin combined with metformin therapy on insulin sensitivity in patients with type 2 diabetes mellitus.European journal of medical research · 2025Article
- Clinical characteristics of Japanese Americans with normal glucose tolerance with 1-h hyperglycemia: A cross-sectional study.Journal of diabetes investigation · 2025Article
- Review
- Dehydration-induced AVP stimulates glucagon release and ketogenesis.American journal of physiology. Endocrinology and metabolism · 2025Article
- The novel antidiabetic medications on diabetic retinopathy: relevant molecular mechanisms, advancing diagnostic innovations, and therapeutic implications.Frontiers in medicine · 2025Review
- Impact of Sodium-Glucose Co-Transporter Type-2 Inhibitors on Alanine Aminotransferase Levels in Type-2 Diabetes Patients Having Features of Nonalcoholic Fatty Liver Disease: A Retrospective Cohort Study in Pakistan.Pakistan journal of medical sciences · 2024Article
- The Impact of SGLT1 Inhibition on Frailty and Sarcopenia: A Mediation Mendelian Randomization Study.Journal of cachexia, sarcopenia and muscle · 2024Article
- The relationship between SGLT2 and systemic blood pressure regulation.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Advances in clinical research on glucagon.Diabetology international · 2024Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesIt is controversial whether sodium glucose transporter (SGLT) 2 inhibitors increase glucagon secretion via direct inhibition of SGLT2 in pancreatic α cells. The role of SGLT1 in α cells is also unclear. We aimed to elucidate these points that are important not only for basic research but also for clinical insight.
methodsPlasma glucagon levels were assessed in the high-fat, high-sucrose diet (HFHSD) fed C57BL/6J mice treated with dapagliflozin or canagliflozin. RT-PCR, RNA sequence, and immunohistochemistry were conducted to test the expression of SGLT1 and SGLT2 in α cells. We also used αTC1 cells and mouse islets to investigate the molecular mechanism by which SGLT1 modulates glucagon secretion.
resultsDapagliflozin, but not canagliflozin, increased plasma glucagon levels in HFHSD fed mice. SGLT1 and glucose transporter 1 (GLUT1), but not SGLT2, were expressed in αTC1 cells, mouse islets and human islets. A glucose clamp study revealed that the plasma glucagon increase associated with dapagliflozin could be explained as a response to acute declines in blood glucose. Canagliflozin suppressed glucagon secretion by inhibiting SGLT1 in α cells; consequently, plasma glucagon did not increase with canagliflozin, even though blood glucose declined. SGLT1 effect on glucagon secretion depended on glucose transport, but not glucose metabolism. Islets from HFHSD and db/db mice displayed higher SGLT1 mRNA levels and lower GLUT1 mRNA levels than the islets from control mice. These expression levels were associated with higher glucagon secretion. Furthermore, SGLT1 inhibitor and siRNA against SGLT1 suppressed glucagon secretion in isolated islets.
conclusionsThese data suggested that a novel mechanism regulated glucagon secretion through SGLT1 in α cells. This finding possibly explained the distinct effects of dapagliflozin and canagliflozin on plasma glucagon levels in mice.
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