ArticleDiabetologia2020
Luseogliflozin increases beta cell proliferation through humoral factors that activate an insulin receptor- and IGF-1 receptor-independent pathway.
Article in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Sweet relief: exploring mechanisms and therapeutic approaches of sodium-glucose cotransporter-2 inhibitors in cardiovascular-kidney metabolic syndrome.Cardiovascular diabetology · 2026Review
- The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner.iScience · 2025Article
- Role of transcription factor FOXM1 in diabetes and its complications (Review).International journal of molecular medicine · 2023Article
- Signaling pathways that regulate adaptive β-cell proliferation for the treatment of diabetes.Journal of diabetes investigation · 2023Review
- Selective BD2 Inhibitor Exerts Anti-Fibrotic Effects via BRD4/FoxM1/Plk1 Axis in Orbital Fibroblasts From Patients With Thyroid Eye Disease.Investigative ophthalmology & visual science · 2023Article
- FOXM1: Functional Roles of FOXM1 in Non-Malignant Diseases.Biomolecules · 2023Review
- E2F1 transcription factor mediates a link between fat and islets to promote β cell proliferation in response to acute insulin resistance.Cell reports · 2022Article
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- Effects of Sodium-Glucose Co-Transporter-2 Inhibitors on Pancreatic β-Cell Mass and Function.International journal of molecular sciences · 2022Review
- Novel Approaches to Restore Pancreatic Beta-Cell Mass and Function.Handbook of experimental pharmacology · 2022Review
- Translational research on human pancreatic β-cell mass expansion for the treatment of diabetes.Diabetology international · 2021Review
- Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice.Scientific reports · 2021Article
- The Roles of the IGF Axis in the Regulation of the Metabolism: Interaction and Difference between Insulin Receptor Signaling and IGF-I Receptor Signaling.International journal of molecular sciences · 2021Review
- Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class.International journal of molecular sciences · 2021Review
- Linagliptin Ameliorates Hepatic Steatosis via Non-Canonical Mechanisms in Mice Treated with a Dual Inhibitor of Insulin Receptor and IGF-1 Receptor.International journal of molecular sciences · 2020Article
- Dapagliflozin Does Not Directly Affect Human α or β Cells.Endocrinology · 2020Article
- Effect of Dapagliflozin on Glycemic Variability in Patients with Type 2 Diabetes under Insulin Glargine Combined with Other Oral Hypoglycemic Drugs.Journal of diabetes research · 2020Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
aims/hypothesisSodium-glucose cotransporter 2 (SGLT2) inhibitors, which prevent the renal reabsorption of glucose, decrease blood glucose levels in an insulin-independent manner. We previously reported creating a mouse model of systemic inhibition of target receptors for both insulin and IGF-1 by treating animals with OSI-906, a dual insulin/IGF-1 receptor inhibitor, for 7 days. The OSI-906-treated mice exhibited an increased beta cell mass, hepatic steatosis and adipose tissue atrophy, accompanied by hyperglycaemia and hyperinsulinaemia. In the present study, we investigated the effects of an SGLT2 inhibitor, luseogliflozin, on these changes in OSI-906-treated mice.
methodsWe treated C57BL/6J male mice either with vehicle, luseogliflozin, OSI-906 or OSI-906 plus luseogliflozin for 7 days, and phenotyping was performed to determine beta cell mass and proliferation. Subsequently, we tested whether serum-derived factors have an effect on beta cell proliferation in genetically engineered beta cells, mouse islets or human islets.
resultsSGLT2 inhibition with luseogliflozin significantly ameliorated hyperglycaemia, but not hyperinsulinaemia, in the OSI-906-treated mice. Liver steatosis and adipose tissue atrophy induced by OSI-906 were not altered by treatment with luseogliflozin. Beta cell mass and proliferation were further increased by SGLT2 inhibition with luseogliflozin in the OSI-906-treated mice. Luseogliflozin upregulated gene expression related to the forkhead box M1 (FoxM1)/polo-like kinase 1 (PLK1)/centromere protein A (CENP-A) pathway in the islets of OSI-906-treated mice. The increase in beta cell proliferation was recapitulated in a co-culture of Irs2 knockout and Insr/IR knockout (βIRKO) beta cells with serum from both luseogliflozin- and OSI-906-treated mice, but not after SGLT2 inhibition in beta cells. Circulating factors in both luseogliflozin- and OSI-906-treated mice promoted beta cell proliferation in both mouse islets and cadaveric human islets. CONCLUSIONS/
interpretationThese results suggest that luseogliflozin can increase beta cell proliferation through the activation of the FoxM1/PLK1/CENP-A pathway via humoral factors that act in an insulin/IGF-1 receptor-independent manner.
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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.