Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Advances in β cell replacement and regeneration strategies for treating diabetes
Jacqueline R. Benthuysen, … , Andrea C. Carrano, Maike Sander
Jacqueline R. Benthuysen, … , Andrea C. Carrano, Maike Sander
Published October 3, 2016
Citation Information: J Clin Invest. 2016;126(10):3651-3660. https://doi.org/10.1172/JCI87439.
View: Text | PDF
Review

Advances in β cell replacement and regeneration strategies for treating diabetes

  • Text
  • PDF
Abstract

In the past decade, new approaches have been explored that are aimed at restoring functional β cell mass as a treatment strategy for diabetes. The two most intensely pursued strategies are β cell replacement through conversion of other cell types and β cell regeneration by enhancement of β cell replication. The approach closest to clinical implementation is the replacement of β cells with human pluripotent stem cell–derived (hPSC-derived) cells, which are currently under investigation in a clinical trial to assess their safety in humans. In addition, there has been success in reprogramming developmentally related cell types into β cells. Reprogramming approaches could find therapeutic applications by inducing β cell conversion in vivo or by reprogramming cells ex vivo followed by implantation. Finally, recent studies have revealed novel pharmacologic targets for stimulating β cell replication. Manipulating these targets or the pathways they regulate could be a strategy for promoting the expansion of residual β cells in diabetic patients. Here, we provide an overview of progress made toward β cell replacement and regeneration and discuss promises and challenges for clinical implementation of these strategies.

Authors

Jacqueline R. Benthuysen, Andrea C. Carrano, Maike Sander

×

Figure 3

Select signaling pathways known to regulate β cell proliferation.

Options: View larger image (or click on image) Download as PowerPoint
Select signaling pathways known to regulate β cell proliferation.
Growth...
Growth factors (PDGF), nutrients (glucose), and hormones (GLP-1 and insulin) have been shown to induce β cell proliferation by activating both canonical and noncanonical mitogenic pathways. Activation of their respective receptors induces signaling via the ERK (also called MAPK) signaling pathway either directly (in the case of PDGF) or via crosstalk mechanisms. Glucose, GLP-1, and insulin have been shown to activate mitogenic signaling via the PI3K/AKT/mTOR pathway. Glucose signals through the calcineurin/NFAT and ERK pathways, while signaling via GLP-1 induces cAMP synthesis to induce proliferation. Small molecules/compounds have been identified that target proteins in these signaling pathways, inhibiting either DYRK1a or GSK3β, both of which phosphorylate NFAT, sequestering it in the cytoplasm. Black and gray arrows indicate canonical and noncanonical signaling, respectively. The depicted pathways regulating β cell proliferation are mainly based on evidence in rodents and do not represent a comprehensive overview of all published work. Compounds shown to induce human β cell replication are indicated in red. AP, aminopyrazine; 5-IT, 5-iodotubercidin; Ca2+, calcium; CN, calcineurin.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts