ArticleThe Journal of biological chemistry2012
FTY720 normalizes hyperglycemia by stimulating β-cell in vivo regeneration in db/db mice through regulation of cyclin D3 and p57(KIP2).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- p21-Activated Kinase 1 (Pak1) as an Element in Functional and Dysfunctional Interplay Among the Myocardium, Adipose Tissue, and Pancreatic Beta Cells.Comprehensive Physiology · 2025Review
- Sphingosine 1-Phosphate Regulates Obesity and Glucose Homeostasis.International journal of molecular sciences · 2024Review
- Therapeutic Potential of Fingolimod in Diabetes Mellitus and Its Chronic Complications.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Fingolimod Modulates the Gene Expression of Proteins Engaged in Inflammation and Amyloid-Beta Metabolism and Improves Exploratory and Anxiety-Like Behavior in Obese Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Is 14-3-3 the Combination to Unlock New Pathways to Improve Metabolic Homeostasis and β-Cell Function?Diabetes · 2023Review
- Regeneration of Pancreatic Beta Cells by Modulation of Molecular Targets Using Plant-Derived Compounds: Pharmacological Mechanisms and Clinical Potential.Current issues in molecular biology · 2023Review
- FTY720-P, a Biased S1PR Ligand, Increases Mitochondrial Function through STAT3 Activation in Cardiac Cells.International journal of molecular sciences · 2023Article
- Immunomodulator FTY720 improves glucose homeostasis and diabetic complications by rejuvenation of β-cell function in nonhuman primate model of diabetes.Fundamental & clinical pharmacology · 2022Article
- 14-3-3ζ Constrains insulin secretion by regulating mitochondrial function in pancreatic β cells.JCI insight · 2022Article
- The small molecule kobusone can stimulate islet β-cell replicationThe Journal of international medical research · 2021Article
- S1P Signaling Pathways in Pathogenesis of Type 2 Diabetes.Journal of diabetes research · 2021Article
- Fingolimod inhibits multiple stages of the HIV-1 life cycle.PLoS pathogens · 2020Article
- Plasma sphingosine 1-phosphate concentrations and cardiovascular autonomic neuropathy in individuals with type 2 diabetes.Scientific reports · 2020Article
- Apolipoprotein M and Sphingosine-1-Phosphate: A Potentially Antidiabetic Tandem Carried by HDL.Diabetes · 2020Article
- FTY720, a sphingosine analog, altered placentome histoarchitecture in ewes.Journal of animal science and biotechnology · 2020Article
- Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication.Journal of lipid research · 2019Review
- Genetic and Epigenetic Control of CDKN1C Expression: Importance in Cell Commitment and Differentiation, Tissue Homeostasis and Human Diseases.International journal of molecular sciences · 2018Review
- Could α-Synuclein Modulation of Insulin and Dopamine Identify a Novel Link Between Parkinson's Disease and Diabetes as Well as Potential Therapies?Frontiers in molecular neuroscience · 2018Review
- The role of sphingolipid signalling in diabetes‑associated pathologies (Review).International journal of molecular medicine · 2017Review
- FoxO1 Plays an Important Role in Regulating β-Cell Compensation for Insulin Resistance in Male Mice.Endocrinology · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Loss of insulin-producing β-cell mass is a hallmark of type 2 diabetes in humans and diabetic db/db mice. Pancreatic β-cells can modulate their mass in response to a variety of physiological and pathophysiological cues. There are currently few effective therapeutic approaches targeting β-cell regeneration although some anti-diabetic drugs may positively affect β-cell mass. Here we show that oral administration of FTY720, a sphingosine 1-phosphate (S1P) receptor modulator, to db/db mice normalizes fasting blood glucose by increasing β-cell mass and blood insulin levels without affecting insulin sensitivity. Fasting blood glucose remained normal in the mice even after the drug was withdrawn after 23 weeks of treatment. The islet area in the pancreases of the FTY720-treated db/db mice was more than 2-fold larger than that of the untreated mice after 6 weeks of treatment. Furthermore, BrdU incorporation assays and Ki67 staining demonstrated cell proliferation in the islets and pancreatic duct areas. Finally, islets from the treated mice exhibited a significant decrease in the level of cyclin-dependent kinase inhibitor p57(KIP2) and an increase in the level of cyclin D3 as compared with those of untreated mice, which could be reversed by the inhibition of phosphatidylinositol 3-kinase (PI3K). Our findings reveal a novel network that controls β-cell regeneration in the obesity-diabetes setting by regulating cyclin D3 and p57(KIP2) expression through the S1P signaling pathway. Therapeutic strategies targeting this network may promote in vivo regeneration of β-cells in patients and prevent and/or cure type 2 diabetes.
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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.