Adenoviral gene transfer of key β cell developmental regulators including Pdx1, Neurod1, and Mafa (PDA) has been reported to generate insulin-producing cells in the liver. However, PDA insulin secretion is transient and glucose unresponsive. Here, we report that an additional β cell developmental regulator, insulin gene enhancer binding protein splicing variant (Isl1β), improved insulin production and glucose-responsive secretion in PDA mice. Microarray gene expression analysis suggested that adenoviral PDA transfer required an additional element for mature β cell generation, such as Isl1 and Elf3 in the liver. In vitro promoter analysis indicated that splicing variant Isl1, or Isl1β, is an important factor for transcriptional activity of the insulin gene. In vivo bioluminescence monitoring using insulin promoter-luciferase transgenic mice verified that adenoviral PDA + Isl1β transfer produced highly intense luminescence from the liver, which peaked at day 7 and persisted for more than 10 days. Using insulin promoter-GFP transgenic mice, we further confirmed that Isl1β supplementation to PDA augmented insulin-producing cells in the liver, insulin production and secretion, and β cell‒related genes. Finally, the PDA + Isl1β combination ameliorated hyperglycemia in diabetic mice for 28 days and enhanced glucose tolerance and responsiveness. Thus, our results suggest that Isl1β is a key additional transcriptional factor for advancing the generation of insulin-producing cells in the liver in combination with PDA.
Pubmed ID: 29220426 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets Islet-1 homeobox
View all literature mentionsThis polyclonal targets B-Actin HRP-DirecT
View all literature mentionsThis polyclonal targets ELF3, aa 375-552
View all literature mentionsThis polyclonal targets NEUROD1
View all literature mentionsThis polyclonal targets Insulin
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal secondary targets IgG1
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on August 26,2019. In October 2016, T1DBase has merged with its sister site ImmunoBase (https://immunobase.org). Documented on March 2020, ImmunoBase ownership has been transferred to Open Targets (https://www.opentargets.org). Results for all studies can be explored using Open Targets Genetics (https://genetics.opentargets.org). Database focused on genetics and genomics of type 1 diabetes susceptibility providing a curated and integrated set of datasets and tools, across multiple species, to support and promote research in this area. The current data scope includes annotated genomic sequences for suspected T1D susceptibility regions; genetic data; microarray data; and global datasets, generally from the literature, that are useful for genetics and systems biology studies. The site also includes software tools for analyzing the data.
View all literature mentionsA web application creating Venn diagrams from two or three gene lists.
View all literature mentionsA desktop application for the analysis, visualization and data-mining of large-scale genomic data. It is a versatile microarray tool, incorporating sophisticated algorithms for clustering, visualization, classification, statistical analysis and biological theme discovery. MeV generates informative and interrelated displays of expression and annotation data from single or multiple experiments. A huge array of alrogithms are included in MeV modules, and are available at a button-click, such as K-means clustering, Hierarchical clustering, t-Tests, Significance Analysis of Microarrays, Gene Set Enrichment Analysis, and EASE. Extensive documentation is available for helping new users get started with MeV. A Quickstart Guide provides the tutorial a brand new person will need to get their first dataset loaded and displayed in the program. Returning MEV users will want to check out the release notes to see what new features are available in the latest versions of the program. Tutorials have been written about several of its more involved features.
View all literature mentionsOpen, web-based platform providing bioinformatics tools and services for data intensive genomic research. Platform may be used as a service or installed locally to perform, reproduce, and share complete analyses. Galaxy automatically tracks and manages data provenance and provides support for capturing the context and intent of computational methods. Galaxy Community has created Galaxy instances in many different forms and for many different applications including Galaxy servers, cloud services that support Galaxy instances, and virtual machines and containers that can be easily deployed for your own server.The Galaxy team is a part of BX at Penn State, and the Biology and Mathematics and Computer Science departments at Emory University.Training Infrastructure as a Service (TIaaS) is a service offered by some UseGalaxy servers to specifically support training use cases.
View all literature mentionsMus musculus with name FVB/N-Tg(Ins1-luc)VUPwrs/J from IMSR.
View all literature mentionsThis monoclonal targets Islet-1 homeobox
View all literature mentionsThis monoclonal targets Islet-1 homeobox
View all literature mentionsThis monoclonal targets Islet-1 homeobox
View all literature mentionsThis polyclonal targets B-Actin HRP-DirecT
View all literature mentionsThis monoclonal targets Islet-1 homeobox
View all literature mentionsThis polyclonal targets B-Actin HRP-DirecT
View all literature mentionsThis polyclonal targets ELF3, aa 375-552
View all literature mentionsThis polyclonal targets NEUROD1
View all literature mentionsThis polyclonal targets ELF3, aa 375-552
View all literature mentionsThis polyclonal targets NEUROD1
View all literature mentionsThis monoclonal targets Islet-1 homeobox
View all literature mentions