ArticleDiabetologia2005
In vitro generation of insulin-producing beta cells from adult exocrine pancreatic cells.
Article in Diabetologia, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed.
- Pancreatic tissue engineering: towards a vascularized bioengineered cure for diabetes.Frontiers in transplantation · 2026Review
- Drug-induced regeneration of pancreatic beta cells: An approach to cellular therapeutic targets.Cell regeneration (London, England) · 2025Review
- Insulin in Myenteric Neurons: Time-Dependent and Regional Changes in Type 1 Diabetic Rats.Cells · 2025Article
- Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status.Signal transduction and targeted therapy · 2025Review
- Lack of glycemic control in type two diabetes mellitus patients is associated with reduced serum epidermal growth factor level and increased insulin resistance.Biomedical reports · 2025Article
- β-Cell Heterogeneity and Plasticity.Advances in anatomy, embryology, and cell biology · 2024Review
- Advanced therapy to cure diabetes: mission impossible is now possible?Frontiers in cell and developmental biology · 2024Review
- β-Cell Regeneration Is Driven by Pancreatic Plasticity.Advances in anatomy, embryology, and cell biology · 2024Review
- An Integrative Approach to the Current Treatment of HIV-Associated Neurocognitive Disorders and the Implementation of Leukemia Inhibitor Factor as a Mediator of Neurocognitive Preservation.Life (Basel, Switzerland) · 2023Review
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- Glucagon- and insulin-immunopositive endocrine cells in porcine extrahepatic bile ducts and gallbladder.Frontiers in veterinary science · 2023Article
- Direct Reprogramming of Somatic Cells into Induced β-Cells: An Overview.Advances in experimental medicine and biology · 2023Article
- Direct Reprogramming of Different Cell Lineages into Pancreatic β-Like Cells.Cellular reprogramming · 2022Review
- Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration.International journal of molecular sciences · 2022Article
- Review
- β cell regeneration and novel strategies for treatment of diabetes (Review).Biomedical reports · 2022Review
- Dysregulated insulin secretion is associated with pancreatic β-cell hyperplasia and direct acinar-β-cell trans-differentiation in partially eNOS-deficient mice.Physiological reports · 2022Article
- Pancreatic β-Cell Development and Regeneration.Cold Spring Harbor perspectives in biology · 2022Review
- Targeting β-cell dedifferentiation and transdifferentiation: opportunities and challenges.Endocrine connections · 2021Review
- Review
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisTransplantation of insulin-producing beta cells from donors can cure diabetes, but they are available in insufficient quantities. In this study, we investigated the possibility of generating insulin-producing cells from adult rat exocrine cells cultured in the presence of growth factors.
methodsRat exocrine pancreatic cells were isolated and treated in vitro with epidermal growth factor (EGF) and leukaemia inhibitory factor (LIF). Analysis was performed by immunocytochemistry, DNA measurement and radioimmunoassay. Cells were transplanted to alloxan-treated (70 mg/kg) nude mice and glycaemia was monitored for 21 days. Nephrectomy was performed on day 15.
resultsIn a 3-day culture period, addition of LIF plus EGF to the medium resulted in an 11-fold increase of the beta cell mass. This could not be attributed to the very low mitotic activity of contaminating beta cells. Furthermore, when contaminating beta cells were initially destroyed with alloxan, this effect was even more pronounced. The newly formed cells secreted insulin in response to glucose and were immunoreactive for C-peptide-I, Pdx-1 and GLUT-2, which are characteristics of mature beta cells. Electron microscopy showed that they also contained insulin-immunoreactive secretory granules. Some insulin-positive cells were immunoreactive for amylase and cytokeratin-20, or were binucleated, which are characteristics of exocrine cells. The cells were able to restore normoglycaemia when transplanted to alloxan-diabetic mice, and hyperglycaemia recurred upon removal of the graft. CONCLUSIONS/
interpretationOur study shows that functional beta cells can be generated from exocrine tissue by transdifferentiation and thereby may offer a new perspective for beta cell therapy.
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Registered trials
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