ArticleScientific reports2021
Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The trial behind it
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Small molecules promote the in vitro expansion and passaging of adult mouse pancreatic islets.Biochemistry and biophysics reports · 2026Article
- The protein deacetylase SIRT2 exerts metabolic control over adaptive β cell proliferation.The Journal of clinical investigation · 2025Article
- Islet single-cell transcriptomic profiling during obesity-induced beta cell expansion in female mice.iScience · 2025Article
- Article
- CLEC11A improves insulin secretion and promotes cell proliferation in human beta-cells.Journal of molecular endocrinology · 2023Article
- Therapeutic Strategies Targeting Pancreatic Islet β-Cell Proliferation, Regeneration, and Replacement.Endocrinology · 2022Article
- β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood.JCI insight · 2022Article
- Small-molecule discovery in the pancreatic beta cell.Current opinion in chemical biology · 2022Review
- Limited extent and consequences of pancreatic SARS-CoV-2 infection.Cell reports · 2022Article
- Evaluation of the Effects of Harmine on β-cell Function and Proliferation in Standardized Human Islets Using 3D High-Content Confocal Imaging and Automated Analysis.Frontiers in endocrinology · 2022Review
- Harnessing Proliferation for the Expansion of Stem Cell-Derived Pancreatic Cells: Advantages and Limitations.Frontiers in endocrinology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The potential to treat diabetes by increasing beta-cell mass is driving a major effort to identify beta-cell mitogens. Demonstration of mitogen activity in human beta cells is frequently performed in ex vivo assays. However, reported disparities in the efficacy of beta-cell mitogens led us to investigate the sources of this variability. We studied 35 male (23) and female (12) human islet batches covering a range of donor ages and BMI. Islets were kept intact or dispersed into single cells and cultured in the presence of harmine, glucose, or heparin-binding epidermal growth factor-like growth factor (HB-EGF), and subsequently analyzed by immunohistochemistry or flow cytometry. Proliferating cells were identified by double labeling with EdU and Ki67 and glucagon, c-peptide or Nkx6.1, and cytokeratin-19 to respectively label alpha, beta, and ductal cells. Harmine and HB-EGF stimulated human beta-cell proliferation, but the effect of glucose was dependent on the assay and the donor. Harmine potently stimulated alpha-cell proliferation and both harmine and HB-EGF increased proliferation of insulin- and glucagon-negative cells, including cytokeratin 19-positive cells. Given the abundance of non-beta cells in human islet preparations, our results suggest that assessment of beta-cell mitogens requires complementary approaches and rigorous identification of cell identity using multiple markers.
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