ArticleDiabetes2010
In vivo expression of HGF/NK1 and GLP-1 From dsAAV vectors enhances pancreatic ß-cell proliferation and improves pathology in the db/db mouse model of diabetes.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Evaluation of transduction efficiency in pancreatic beta and alpha cells utilizing various AAV serotypes.Scientific reports · 2025Article
- A comprehensive atlas of AAV tropism in the mouse.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Dimer Interface in Natural Variant NK1 Is Dispensable for HGF-Dependent Met Receptor Activation.International journal of molecular sciences · 2021Article
- Debates in Pancreatic Beta Cell Biology: Proliferation Versus Progenitor Differentiation and Transdifferentiation in Restoring β Cell Mass.Frontiers in endocrinology · 2021Review
- Adipose Tissue-Derived Stem Cells from Type 2 Diabetics Reveal Conservative Alterations in Multidimensional Characteristics.International journal of stem cells · 2020Article
- AAV GCG-EGFP, a new tool to identify glucagon-secreting α-cells.Scientific reports · 2019Article
- Endogenous Pancreatic β Cell Regeneration: A Potential Strategy for the Recovery of β Cell Deficiency in Diabetes.Frontiers in endocrinology · 2019Review
- Antibody-mediated oral delivery of therapeutic DNA for type 2 diabetes mellitus.Biomaterials research · 2018Article
- Transgene and islet cell delivery systems using nano-sized carriers for the treatment of diabetes mellitus.Nano reviews & experiments · 2017Review
- One-time injection of AAV8 encoding urocortin 2 provides long-term resolution of insulin resistance.JCI insight · 2016Article
- Article
- In vivo pancreatic β-cell-specific expression of antiaging gene Klotho: a novel approach for preserving β-cells in type 2 diabetes.Diabetes · 2015Article
- Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling.Biomedicines · 2014Review
- AAV-mediated gene therapy for atherosclerosis.Current atherosclerosis reports · 2014Review
- Islet cell plasticity and regeneration.Molecular metabolism · 2014Review
- Global gene expression profiling of pancreatic islets in mice during streptozotocin-induced β-cell damage and pancreatic Glp-1 gene therapy.Disease models & mechanisms · 2013Article
- Prenatal expression of MET receptor tyrosine kinase in the fetal mouse dorsal raphe nuclei and the visceral motor/sensory brainstem.Developmental neuroscience · 2013Article
- dsAAV8-mediated gene transfer and β-cell expression of IL-4 and β-cell growth factors are capable of reversing early-onset diabetes in NOD mice.Gene therapy · 2012Article
- The global transcriptional response of isolated human islets of langerhans to glucagon-like Peptide-1 receptor agonist liraglutide.ISRN endocrinology · 2012Article
- Immunomodulation of antigen presenting cells promotes natural regulatory T cells that prevent autoimmune diabetes in NOD mice.PloS one · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe purpose of the current study was to determine whether double-stranded adeno-associated virus (dsAAV)-mediated in vivo expression of β-cell growth factors, glucagon-like peptide-1 (GLP-1) and the NK1 fragment of hepatocyte growth factor (HGF/NK1) in β-cells, improves pathology in the db/db mouse model of type 2 diabetes. RESEARCH DESIGN AND METHODS; The glucoregulatory actions of GLP-1 and full-length HGF are well characterized. Here, we test the ability of HGF/NK1 to induce proliferation of exogenous islets and MIN6 β-cells. In addition, we target both GLP-1 and HGF/NK1 to endogenous β-cells using dsAAV vectors containing the mouse insulin-II promoter. We compare the abilities of these gene products to induce islet proliferation in vitro and in vivo and characterize their abilities to regulate diabetes after AAV-mediated delivery to endogenous islets of db/db mice.
resultsRecombinant HGF/NK1 induces proliferation of isolated islets, and dsAAV-mediated expression of both GLP-1 and HGF/NK1 induces significant β-cell proliferation in vivo. Furthermore, both GLP-1 and HGF/NK1 expressed from dsAAV vectors enhance β-cell mass and insulin secretion in vivo and significantly delay the onset of hyperglycemia in db/db mice.
conclusionsA single treatment with dsAAV vectors expressing GLP-1 or HGF/NK1 enhances islet growth and significantly improves pathology in a mouse model of type 2 diabetes. This represents the first example of a successful use of HGF/NK1 for diabetes therapy, providing support for direct AAV-mediated in vivo delivery of β-cell growth factors as a novel therapeutic strategy for the treatment of type 2 diabetes.
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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.