ArticleThe Journal of clinical investigation2022
Pharmacological conversion of gut epithelial cells into insulin-producing cells lowers glycemia in diabetic animals.
Article in The Journal of clinical investigation, 2022. 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, 27 citations in OpenAlex.
- IL-22 increases proglucagon-expressing enteroendocrine cells via STAT3 in human iPSC-derived intestinal epithelium.Endocrinology · 2026Article
- Charting Endocrine Progenitors Across Species and Organs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ferroptosis as a Pathogenic Mechanism and Therapeutic Target in Autoimmune and Inflammatory Skin Diseases.Clinical reviews in allergy & immunology · 2026Review
- Investigational treatments of β-cell failure and replacement.Diabetology international · 2026Review
- The crosstalk between iron metabolism and immune tolerance in autoimmunity.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Gut-Heart Axis in HFpEF: The Emerging Role of Microbiome-Driven Inflammation and Endothelial Dysfunction.Biomolecules · 2026Review
- The Role of Non-coding RNAs in Connective Tissue Diseases: Diagnostic and Therapeutic Potential of miRNAs, lncRNAs and circRNAs.Molecular diagnosis & therapy · 2026Review
- Transcriptome Analysis of Non-coding RNAs and mRNAs in the Dorsal Root Ganglion of Peripheral Nerve Injury-Induced Neuropathic Pain.Biochemical genetics · 2026Article
- Modeling in vivo induction of gastric insulin-secreting cells using transplanted human stomach organoids.Stem cell reports · 2025Article
- Enteroendocrine cell differentiation: Implications for human disease.Molecular and cellular endocrinology · 2025Review
- The signature of the small intestinal epithelial and immune cells in health and diseases.Chinese medical journal · 2025Review
- Mechanistic insights and approaches for beta cell regeneration.Nature chemical biology · 2025Review
- Insulin in Myenteric Neurons: Time-Dependent and Regional Changes in Type 1 Diabetic Rats.Cells · 2025Article
- Carnosic acid attenuates diabetic retinopathy via the SIRT1 signaling pathway: neuroprotection and endothelial cell preservation.American journal of translational research · 2025Article
- Organoids: their emerging essential role in pathological mechanisms and drug discovery of diabetes and its complications.Frontiers in pharmacology · 2025Review
- β-cell heterogeneity and molecular plasticity in type 2 diabetes: multi-omics perspectives and the role of gut microbiota.Frontiers in cell and developmental biology · 2025Review
- Molecular functions of HAX1 during disease progress.Virus genes · 2024Review
- Diabetes treatment by conversion of gut epithelial cells to insulin-producing cells.Journal of diabetes investigation · 2024Review
- Knockdown of SCN5A alters metabolic-associated genes and aggravates hypertrophy in the cardiomyoblast.Molecular biology reports · 2024Article
- Application and challenge of pancreatic organoids in therapeutic research.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 1 country.
Funding
Abstract
As a highly regenerative organ, the intestine is a promising source for cellular reprogramming for replacing lost pancreatic β cells in diabetes. Gut enterochromaffin cells can be converted to insulin-producing cells by forkhead box O1 (FoxO1) ablation, but their numbers are limited. In this study, we report that insulin-immunoreactive cells with Paneth/goblet cell features are present in human fetal intestine. Accordingly, lineage-tracing experiments show that, upon genetic or pharmacologic FoxO1 ablation, the Paneth/goblet lineage can also undergo conversion to the insulin lineage. We designed a screening platform in gut organoids to accurately quantitate β-like cell reprogramming and fine-tune a combination treatment to increase the efficiency of the conversion process in mice and human adult intestinal organoids. We identified a triple blockade of FOXO1, Notch, and TGF-β that, when tested in insulin-deficient streptozotocin (STZ) or NOD diabetic animals, resulted in near normalization of glucose levels, associated with the generation of intestinal insulin-producing cells. The findings illustrate a therapeutic approach for replacing insulin treatment in diabetes.
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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.