ArticleEndocrinology2010
Insulinoma-associated antigen-1 zinc-finger transcription factor promotes pancreatic duct cell trans-differentiation.
Article in Endocrinology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- NEUROD1: transcriptional and epigenetic regulator of human and mouse neuronal and endocrine cell lineage programs.Frontiers in cell and developmental biology · 2024Review
- High expression of insulinoma-associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrine carcinomas from conventional adenocarcinomas with diffuse expression of synaptophysin.The journal of pathology. Clinical research · 2023Article
- Review
- INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists' View.Diagnostics (Basel, Switzerland) · 2021Review
- Article
- Article
- Detecting cell-type-specific allelic expression imbalance by integrative analysis of bulk and single-cell RNA sequencing data.PLoS genetics · 2021Article
- An Algorithmic Immunohistochemical Approach to Define Tumor Type and Assign Site of Origin.Advances in anatomic pathology · 2020Review
- A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1.Cancers · 2020Article
- Immunohistochemistry in the diagnosis and classification of neuroendocrine neoplasms: what can brown do for you?Human pathology · 2020Review
- Insulinoma-Associated-1: From Neuroendocrine Tumor Marker to Cancer Therapeutics.Molecular cancer research : MCR · 2019Review
- Alleles of Insm1 determine whether RIP1-Tag2 mice produce insulinomas or nonfunctioning pancreatic neuroendocrine tumors.Oncogenesis · 2019Article
- Targeted deletion of Insm2 in mice result in reduced insulin secretion and glucose intolerance.Journal of translational medicine · 2018Article
- Gene expression signature predicts human islet integrity and transplant functionality in diabetic mice.PloS one · 2017Article
- Article
- β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells.Therapeutic advances in endocrinology and metabolism · 2016Review
- Extra-nuclear activity of INSM1 transcription factor enhances insulin receptor signaling pathway and Nkx6.1 expression through RACK1 interaction.Cellular signalling · 2014Article
- Transcription factor ZBED6 affects gene expression, proliferation, and cell death in pancreatic beta cells.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Snail/Gfi-1 (SNAG) family zinc finger proteins in transcription regulation, chromatin dynamics, cell signaling, development, and disease.Cytokine & growth factor reviews · 2013Review
- Functional role of an islet transcription factor, INSM1/IA-1, on pancreatic acinar cell trans-differentiation.Journal of cellular physiology · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Insulinoma-associated antigen-1 (INSM1/IA-1) is a unique zinc-finger transcription factor restrictedly expressed in pancreatic beta-cells during early pancreas development. INSM1 is transiently activated by the islet-specific endocrine factor neurogenin 3, and it subsequently regulates downstream target genes NeuroD1 and insulin during beta-cell maturation. Here, we examined how the INSM1 transcription factor contributes to endocrine cell differentiation using a defined serum-free medium-primed pancreatic duct cell model. We showed that ectopic expression of INSM1 can promote Panc-1 cell trans-differentiation. INSM1 up-regulates two islet transcription factors (ITFs), paired box 6 and homeodomain transcription factor 6.1, whereas other ITFs, including pancreatic duodenal homeobox-1 (Pdx-1), homeodomain transcription factor 2.2, NeuroD1, paired box 4, and neurogenin 3, were either down-regulated or absent. The result suggests that INSM1 is capable of regulating multiple ITFs and the insulin gene either directly or indirectly. When we overexpressed three ITFs, INSM1/Pdx-1/NeuroD1, in the Panc-1 differentiation model, higher insulin expression was observed in parallel with the activation of an additional ITF, neurogenin 3, signifying endocrine cell activation. Insulin expression from the three ITFs stimulation was readily detected by immunostaining and increased 40% as compared with the insulin-transferrin-selenium-LacZ control. Furthermore, we examined the differential chromatin acetylation patterns within the insulin promoter region using the chromatin immunoprecipitation assay. INSM1 alone can selectively enhance acetylation of histone H4, whereas NeuroD1 and Pdx-1 favor the acetylation of histone H3. Both H3 and H4 histone acetylations facilitate insulin gene expression. The consistent functional effect of INSM1, either with or without other ITFs, promotes pancreatic duct cell differentiation as well as induces Panc-1 cell cycle arrest.
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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.