ArticleDiabetologia2015
Activation of GLP-1 and gastrin signalling induces in vivo reprogramming of pancreatic exocrine cells into beta cells in mice.
Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- CCKBR signalling controls human definitive endoderm specification and pancreatic lineage differentiation.Diabetologia · 2026Article
- New discoveries in therapeutic targets and drug development pathways for type 2 diabetes mellitus under the guidance of precision medicine.European journal of medical research · 2025Review
- Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments.Pharmacological reviews · 2025Review
- Efficacy evaluation and mechanistic investigation of transcutaneous auricular vagus nerve stimulation in enhancing the therapeutic effects of semaglutide and reducing its gastrointestinal side effects: a randomized controlled trial protocol.Frontiers in neurology · 2025Article
- Oral tolerogenic vaccine combined with gastrin restores immune tolerance and beta-cell function in NOD mice with Type 1 diabetes.Frontiers in immunology · 2025Article
- Effect of gut hormones on bone metabolism and their possible mechanisms in the treatment of osteoporosis.Frontiers in pharmacology · 2024Review
- Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment.Open medicine (Warsaw, Poland) · 2023Article
- STAT3 suppression and β-cell ablation enhance α-to-β reprogramming mediated by Pdx1.Scientific reports · 2022Article
- Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes.Autoimmunity · 2022Article
- Small Molecule-Induced Pancreatic β-Like Cell Development: Mechanistic Approaches and Available Strategies.International journal of molecular sciences · 2020Review
- Marked Hypergastrinemia with G-cell Hyperplasia in Two Autoimmune Gastritis Patients.Internal medicine (Tokyo, Japan) · 2020Article
- Low-Dose Decitabine Assists Human Umbilical Cord-Derived Mesenchymal Stem Cells in ProtectingStem cells international · 2020Article
- Insulin-Producing Cell Transplantation Platform for Veterinary Practice.Frontiers in veterinary science · 2020Review
- Pathological Mechanisms in Diabetes of the Exocrine Pancreas: What's Known and What's to Know.Frontiers in physiology · 2020Review
- Glucagon-Like Peptide-1 Receptor Agonist Protects Dorsal Root Ganglion Neurons against Oxidative Insult.Journal of diabetes research · 2019Article
- A New Way for Beta Cell Neogenesis: Transdifferentiation from Alpha Cells Induced by Glucagon-Like Peptide 1.Journal of diabetes research · 2019Article
- Suppression of STAT3 signaling promotes cellular reprogramming into insulin-producing cells induced by defined transcription factors.EBioMedicine · 2018Article
- The potential and challenges of alternative sources of β cells for the cure of type 1 diabetes.Endocrine connections · 2018Review
- Mesenchymal stem cell therapy in type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2017Review
- The Impact of Glucagon-Like Peptide-1 on Bone Metabolism and Its Possible Mechanisms.Frontiers in endocrinology · 2017Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
aims/hypothesisLineage conversion of non-beta cells into insulin-producing cells has been proposed as a therapy for the cure of diabetes. Glucagon-like peptide-1 (GLP-1) and its derivatives can induce beta cell neogenesis in vitro and beta cell mass expansion in vivo, but GLP-1 signalling has not been shown to regulate cell fate decisions in vivo. We therefore tested the impact of GLP-1 receptor (GLP1R) expression on beta cell differentiation in vivo.
methodsMice overexpressing GLP1R in pancreatic exocrine cells were generated by Cre-mediated recombination in sex-determining region Y-box 9 (SOX9)-expressing cells and then treated with exendin-4 and/or gastrin. Histological analysis was performed to detect cellular reprogramming from the exocrine lineage into insulin-producing cells.
resultsWhereas no newly generated beta cells were detected in the mice treated with exendin-4 alone, treatment with gastrin only induced the conversion of exocrine cells into insulin-producing cells. Furthermore, the overexpression of GLP1R, together with gastrin and exendin-4, synergistically promoted beta cell neogenesis accompanied by the formation of islet-like clusters. These newly generated beta cells expressed beta cell specific transcription factors, such as pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). These mice showed no histological evidence of pancreatitis or pancreatic dysplasia in their acini and had normal plasma amylase levels. CONCLUSIONS/
interpretationActivation of GLP-1 and gastrin signalling induces beta cell neogenesis in the exocrine lineage without any deleterious pancreatic changes, which may lead to a potential therapy to cure diabetes by generating surrogate beta cells.
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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.