ArticleEndocrinology2009
Gene therapy with neurogenin 3 and betacellulin reverses major metabolic problems in insulin-deficient diabetic mice.
Article in Endocrinology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- A review of epidermal growth factor receptor ligands in glucose homeostasis.Frontiers in endocrinology · 2026Review
- Epigen-mediated mechanisms to alleviate glucose homeostasis disruptions in diet-induced obese and STZ-induced diabetic mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- An Insight into Vital Genes Responsible for β-cell Formation.Advances in experimental medicine and biology · 2024Article
- Liver to Pancreas Transdifferentiation.Current diabetes reports · 2019Review
- The potential and challenges of alternative sources of β cells for the cure of type 1 diabetes.Endocrine connections · 2018Review
- Anti-TCRβ mAb in Combination With Neurogenin3 Gene Therapy Reverses Established Overt Type 1 Diabetes in Female NOD Mice.Endocrinology · 2017Article
- Article
- Gene therapy with neurogenin3, betacellulin and SOCS1 reverses diabetes in NOD mice.Gene therapy · 2015Article
- PD-L1-driven tolerance protects neurogenin3-induced islet neogenesis to reverse established type 1 diabetes in NOD mice.Diabetes · 2015Article
- Platelet-derived growth factor BB mimics serum-induced dispersal of pancreatic epithelial cell clusters.Journal of cellular physiology · 2014Article
- Neurogenin3 cooperates with Foxa2 to autoactivate its own expression.The Journal of biological chemistry · 2013Article
- Mechanistic basis of immunotherapies for type 1 diabetes mellitus.Translational research : the journal of laboratory and clinical medicine · 2013Review
- Nkx6.1 controls a gene regulatory network required for establishing and maintaining pancreatic Beta cell identity.PLoS genetics · 2013Article
- Genetically reprogrammed, liver-derived insulin-producing cells are glucose-responsive, but susceptible to autoimmune destruction in settings of murine model of type 1 diabetes.American journal of translational research · 2013Article
- Neo-islet formation in liver of diabetic mice by helper-dependent adenoviral vector-mediated gene transfer.Journal of visualized experiments : JoVE · 2012Article
- Directed differentiation of progenitor cells towards an islet-cell phenotype.American journal of stem cells · 2012Article
- Stem cell approaches for diabetes: towards beta cell replacement.Genome medicine · 2011Article
- Stem cell-based approaches for the treatment of diabetes.Stem cells international · 2011Article
- Stem cell approaches for the treatment of type 1 diabetes mellitus.Translational research : the journal of laboratory and clinical medicine · 2010Review
- Minireview: beta-cell replacement therapy for diabetes in the 21st century: manipulation of cell fate by directed differentiation.Molecular endocrinology (Baltimore, Md.) · 2010Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Insulin deficiency in type 1 diabetes leads to disruptions in glucose, lipid, and ketone metabolism with resultant hyperglycemia, hyperlipidemia, and ketonemia. Exogenous insulin and hepatic insulin gene therapy cannot mimic the robust glucose-stimulated insulin secretion (GSIS) from native pancreatic islets. Gene therapy of streptozotocin-diabetic mice with neurogenin 3 (Ngn3) and betacellulin (Btc) leads to the induction of periportal oval cell-derived neo-islets that exhibit GSIS. We hence hypothesized that this gene therapy regimen may lead to a complete correction of the glucose and lipid metabolic abnormalities associated with insulin deficiency; we further hypothesized that the neo-islets formed in response to Ngn3-Btc gene delivery may display an ultrastructure and transcription profile similar to that of pancreatic islets. We injected streptozotocin-diabetic mice with helper-dependent adenoviral vectors carrying Ngn3 and Btc, which restored GSIS and reversed hyperglycemia in these animals. The treatment also normalized hepatic glucose secretion and reversed ketonemia. Furthermore, it restored hepatic glycogen content and reinstated hepatic lipogenesis-related gene transcripts back to nondiabetic levels. By transmission electron microscopy, the neo-islets displayed electron-dense granules that were similar in appearance to those in pancreatic islets. Finally, using RNA obtained by laser capture microdissection of the periportal neo-islets and normal pancreatic islets, we found that the neo-islets and pancreatic islets exhibited a very similar transcription profile on microarray-based transcriptome analysis. Taken together, this indicates that Ngn3-Btc gene therapy corrects the underlying dysregulated glucose and lipid metabolism in insulin-deficient diabetic mice by inducing neo-islets in the liver that are similar to pancreatic islets in structure and gene expression profile.
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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.