ArticleProceedings of the National Academy of Sciences of the United States of America2016
Growth factors and medium hyperglycemia induce Sox9+ ductal cell differentiation into β cells in mice with reversal of diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 72 citations in OpenAlex.
- Integrative gene target mapping, RNA sequencing, in silico molecular docking, ADMET profiling and molecular dynamics simulation study of marine derived molecules for type 1 diabetes mellitus.Molecular diversity · 2026Article
- SOX9: dosage- and context-dependent functions in pancreatic development and β-cell biology.Cell communication and signaling : CCS · 2026Review
- Review
- Contribution of cytokeratin 19-expressing cells towards islet regeneration induced by multipotent stromal cell secreted proteins.Stem cells (Dayton, Ohio) · 2025Article
- Article
- Pancreatic Ductal Cell Heterogeneity: Insights into the Potential for β-Cell Regeneration in Diabetes.Stem cell reviews and reports · 2025Review
- Differentiation, reduction, and proliferation of pancreatic β-cells and their regulatory factors.Diabetology international · 2025Review
- Effects of Neurogenin 3 Induction on Endocrine Differentiation and Delamination in Adult Human Pancreatic Ductal Organoids.Transplant international : official journal of the European Society for Organ Transplantation · 2025Article
- Hinokione: an abietene diterpene with pancreatic β cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara.Journal of natural medicines · 2024Article
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Acinar to β-like cell conversion through inhibition of focal adhesion kinase.Nature communications · 2024Article
- β-Cell Regeneration Is Driven by Pancreatic Plasticity.Advances in anatomy, embryology, and cell biology · 2024Review
- Hydrogel-Encapsulated Pancreatic Islet Cells as a Promising Strategy for Diabetic Cell Therapy.Research (Washington, D.C.) · 2024Review
- EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors.Signal transduction and targeted therapy · 2024Article
- Species-specific roles for the MAFA and MAFB transcription factors in regulating islet β cell identity.JCI insight · 2023Article
- 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
- Limitations and challenges of direct cell reprogramming in vitro and in vivo.Histology and histopathology · 2022Review
- The m6A methylation profiles of immune cells in type 1 diabetes mellitus.Frontiers in immunology · 2022Article
- Renal subcapsular delivery of PGEiScience · 2021Article
- Ductal Ngn3-expressing progenitors contribute to adult β cell neogenesis in the pancreas.Cell stem cell · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously reported that long-term administration of a low dose of gastrin and epidermal growth factor (GE) augments β-cell neogenesis in late-stage diabetic autoimmune mice after eliminating insulitis by induction of mixed chimerism. However, the source of β-cell neogenesis is still unknown. SRY (sex-determining region Y)-box 9(+) (Sox9(+)) ductal cells in the adult pancreas are clonogenic and can give rise to insulin-producing β cells in an in vitro culture. Whether Sox9(+) ductal cells in the adult pancreas can give rise to β cells in vivo remains controversial. Here, using lineage-tracing with genetic labeling of Insulin- or Sox9-expressing cells, we show that hyperglycemia (>300 mg/dL) is required for inducing Sox9(+) ductal cell differentiation into insulin-producing β cells, and medium hyperglycemia (300-450 mg/dL) in combination with long-term administration of low-dose GE synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. Short-term administration of high-dose GE cannot augment differentiation, although it can augment preexisting β-cell replication. These results indicate that medium hyperglycemia combined with long-term administration of low-dose GE represents one way to induce Sox9(+) ductal cell differentiation into β cells in adult mice.
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