ArticleJournal of cell science2013
Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
37 citing papers in PubMed, 64 citations in OpenAlex.
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- Insulin in Myenteric Neurons: Time-Dependent and Regional Changes in Type 1 Diabetic Rats.Cells · 2025Article
- Identifying antisense oligonucleotides for targeted inhibition of insulin receptor isoform A.Frontiers in oncology · 2025Article
- Mechanisms of Insulin Signaling as a Potential Therapeutic Method in Intestinal Diseases.Cells · 2024Review
- Neonatal enteroids absorb extracellular vesicles from human milk-fed infant digestive fluid.Journal of extracellular vesicles · 2024Article
- Insulin Receptor Isoforms and Insulin Growth Factor-like Receptors: Implications in Cell Signaling, Carcinogenesis, and Chemoresistance.International journal of molecular sciences · 2023Review
- Let-7 microRNAs Are Possibly Associated with Perineural Invasion in Colorectal Cancer by Targeting IGF Axis.Life (Basel, Switzerland) · 2022Article
- Hepatocyte Deletion of IGF2 Prevents DNA Damage and Tumor Formation in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Subventricular zone adult mouse neural stem cells require insulin receptor for self-renewal.Stem cell reports · 2022Article
- Article
- Insulin Receptor Isoforms Differently Regulate Cell Proliferation and Apoptosis in the Ligand-Occupied and Unoccupied State.International journal of molecular sciences · 2021Article
- Mechanisms of Glucose Absorption in the Small Intestine in Health and Metabolic Diseases and Their Role in Appetite Regulation.Nutrients · 2021Review
- Modifying Effects of Glucose and Insulin/Insulin-Like Growth Factors on Colon Cancer Cells.Frontiers in oncology · 2021Article
- Glucose transporters in the small intestine in health and disease.Pflugers Archiv : European journal of physiology · 2020Review
- Molecular Response in Intestinal and Immune Tissues toFrontiers in veterinary science · 2020Article
- Phenformin as an Anticancer Agent: Challenges and Prospects.International journal of molecular sciences · 2019Review
- The Influence of Curcumin on the Downregulation of MYC, Insulin and IGF-1 Receptors: A possible Mechanism Underlying the Anti-Growth and Anti-Migration in Chemoresistant Colorectal Cancer Cells.Medicina (Kaunas, Lithuania) · 2019Article
- Muscleblind‑like 1 destabilizes Snail mRNA and suppresses the metastasis of colorectal cancer cells via the Snail/E‑cadherin axis.International journal of oncology · 2019Article
- Insulin Receptor Isoforms in Cancer.International journal of molecular sciences · 2018Review
- The interplay of BMP4 and IL‑7 regulates the apoptosis of intestinal intraepithelial lymphocytes under conditions of ischemia̸reperfusion.International journal of molecular medicine · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Despite evidence for the impact of insulin on intestinal epithelial physiology and pathophysiology, the expression patterns, roles, and regulation of insulin receptor (IR) and IR isoforms in the intestinal epithelium are not well characterized. IR-A is thought to mediate the proliferative effects of insulin or insulin growth factors (IGFs) in fetal or cancer cells. IR-B is considered to be the metabolic receptor for insulin in specialized tissues. This study used a novel Sox9-EGFP reporter mouse that permits isolation of intestinal epithelial stem cells (IESCs), progenitors, enteroendocrine cells and differentiated lineages, the Apc(Min/+) mouse model of precancerous adenoma and normal human intestinal and colorectal cancer (CRC) cell lines. We tested the hypothesis that there is differential expression of IR-A or IR-B in stem and tumor cells versus differentiated intestinal epithelial cells (IECs) and that IR-B impacts cell proliferation. Our findings provide evidence that IR-B expression is significantly lower in highly proliferative IESCs and progenitor cells versus post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus differentiated Caco-2 cells. IR-B is also reduced in Apc(Min/+) tumors and highly tumorigenic CRC cells. These differences in IR-B were accompanied by altered levels of mRNAs encoding muscleblind-like 2 (MBNL2), a known regulator of IR alternative splicing. Forced IR-B expression in subconfluent and undifferentiated Caco-2 cells reduced proliferation and increased biomarkers of differentiation. Our findings indicate that the impact of insulin on different cell types in the intestinal epithelium might differ depending on relative IR-B IR-A expression levels and provide new evidence for the roles of IR-B to limit proliferation of CRC cells.
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Registered trials
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