ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
PAX4 Gene Transfer Induces α-to-β Cell Phenotypic Conversion and Confers Therapeutic Benefits for Diabetes Treatment.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 59 citations in OpenAlex.
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- Cycling alpha cells in regenerative drug-treated human pancreatic islets may serve as key beta cell progenitors.Cell reports. Medicine · 2024Article
- In Silico Functional and Structural Analysis of Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in Human Paired Box 4 Gene.Biochemical genetics · 2024Article
- PAX4 gene delivery improves β-cell function in human islets of Type II diabetes.Regenerative medicine · 2024Article
- A Case of Maturity-Onset Diabetes of the Young With Complex Mutations.JCEM case reports · 2024Article
- Development, regeneration, and physiological expansion of functional β-cells: Cellular sources and regulators.Frontiers in cell and developmental biology · 2024Review
- An Insight into Vital Genes Responsible for β-cell Formation.Advances in experimental medicine and biology · 2024Article
- Pax4 in Health and Diabetes.International journal of molecular sciences · 2023Review
- Repurposing Pitavastatin and L-Glutamine: Replenishing β-Cells in Hyperlipidemic Type 2 Diabetes Mouse Model.Life (Basel, Switzerland) · 2023Article
- Pax4-Ghrelin mediates the conversion of pancreatic ε-cells to β-cells after extreme β-cell loss in zebrafish.Development (Cambridge, England) · 2023Article
- Alpha-to-beta cell trans-differentiation for treatment of diabetes.Biochemical Society transactions · 2021Review
- The Human Islet: Mini-Organ With Mega-Impact.Endocrine reviews · 2021Review
- Increased NKX6.1 expression and decreased ARX expression in alpha cells accompany reduced beta-cell volume in human subjects.Scientific reports · 2021Article
- A Mouse Model for Chronic Pancreatitis via Bile Duct TNBS Infusion.Journal of visualized experiments : JoVE · 2021Article
- Effects and mechanism of stem cells from human exfoliated deciduous teeth combined with hyperbaric oxygen therapy in type 2 diabetic rats.Clinics (Sao Paulo, Brazil) · 2020Article
- Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors.JCI insight · 2019Article
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6 authors at 2 institutions in 1 country.
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Abstract
The transcription factor Pax4 plays a critical role in the determination of α- versus β-cell lineage during endocrine pancreas development. In this study, we explored whether Pax4 gene transfer into α-cells could convert them into functional β-cells and thus provide therapeutic benefits for insulin-deficient diabetes. We found that Pax4 delivered by adenoviral vector, Ad5.Pax4, induced insulin expression and reduced glucagon expression in αTC1.9 cells. More importantly, these cells exhibited glucose-stimulated insulin secretion, a key feature of functional β-cells. When injected into streptozotocin-induced diabetic mice, Pax4-treated αTC1.9 cells significantly reduced blood glucose, and the mice showed better glucose tolerance, supporting that Pax4 gene transfer into αTC1.9 cells resulted in the formation of functional β-cells. Furthermore, treatment of primary human islets with Ad5.Pax4 resulted in significantly improved β-cell function. Detection of glucagon(+)/Pax4(+)/Insulin(+) cells argued for Pax4-induced α-to-β cell transitioning. This was further supported by quantification of glucagon and insulin bi-hormonal cells, which was significantly higher in Pax4-treated islets than in controls. Finally, direct administration of Ad5.Pax4 into the pancreas of insulin-deficient mice ameliorated hyperglycemia. Taken together, our data demonstrate that manipulating Pax4 gene expression represents a viable therapeutic strategy for the treatment of insulin deficient diabetes.
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