ArticleGene therapy2002
Constitutive and regulated expression of processed insulin following in vivo hepatic gene transfer.
Article in Gene therapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 85 citations in OpenAlex.
- Applications of Genome-Editing Technologies for Type 1 Diabetes.International journal of molecular sciences · 2023Review
- Emerging therapeutic options in the management of diabetes: recent trends, challenges and future directions.International journal of obesity (2005) · 2023Review
- Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update.Journal of diabetes research · 2015Review
- Spatiotemporal control of vascular endothelial growth factor expression using a heat-shock-activated, rapamycin-dependent gene switch.Human gene therapy methods · 2013Article
- Vector and helper genome rearrangements occur during production of helper-dependent adenoviral vectors.Human gene therapy methods · 2013Article
- Article
- Reversal of diabetes through gene therapy of diabetic rats by hepatic insulin expression via lentiviral transduction.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Combinatorial insulin secretion dynamics of recombinant hepatic and enteroendocrine cells.Biotechnology and bioengineering · 2012Article
- PiggyBac transposon-based inducible gene expression in vivo after somatic cell gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Induction of insulin secretion in engineered liver cells by nitric oxide.BMC physiology · 2007Article
- Long-term correction of diabetes in rats after lentiviral hepatic insulin gene therapy.Diabetologia · 2007Article
- Regulatable gene expression systems for gene therapy.Current gene therapy · 2006Review
- Regulatable gene expression systems for gene therapy applications: progress and future challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2005Review
- Plasmid-electroporated primary hepatocytes acquire quasi-physiological secretion of human insulin and restore euglycemia in diabetic mice.Gene therapy · 2005Article
- Enhanced insulin secretion from engineered 3T3-L1 preadipocytes by induction of cellular differentiation.Molecular and cellular biochemistry · 2005Article
- Rapamycin control of exocrine protein levels in saliva after adenoviral vector-mediated gene transfer.Gene therapy · 2004Article
- Gene therapy progress and prospects: transcription regulatory systems.Gene therapy · 2004Review
- Insulin expression in livers of diabetic mice mediated by hydrodynamics-based administration.World journal of gastroenterology · 2004Article
- Viral vectors for gene delivery to the nervous system.Nature reviews. Neuroscience · 2003Review
- Vectors for the treatment of autoimmune disease.Gene therapy · 2003Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
To test whether hepatocytes engineered in vivo can serve as surrogate beta cells by similarly secreting mature insulin in a glucose-sensitive manner, we prepared adenoviral vectors encoding wild-type proinsulin (hIns-wt), a modified proinsulin cleavable by the ubiquitously expressed protease furin (hIns-M3), or each of the two beta cell specific pro-insulin convertases PC2 and PC3. Following a detailed in vitro characterization of the proteins produced by our vectors, we infected the liver and, for comparison, the muscle of a chemically induced murine model of type I diabetes. Insulin expression from the transduced tissues was extensively characterized and showed to be constitutive rather than regulated. To obtain regulated expression, we placed expression of hIns-M3 under the control of the dimerizer-inducible transcription system. Hormone secretion from mouse liver was negligible in the absence of the dimerizer drug rapamycin, was inducible in a dose-dependent manner upon its administration, and reversible following drug withdrawal. These data confirm liver as a promising target for in vivo expression of processed insulin. While suggesting that hepatocytes cannot provide authentic glucose-responsive regulation, these results demonstrate that pharmacological regulation is a promising alternative route to the controlled delivery of insulin following hepatic gene transfer.
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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.