Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Nov;6(11):2039-2053.
doi: 10.1038/s42255-024-01097-6. Epub 2024 Aug 8.

Exploring pancreatic beta-cell subgroups and their connectivity

Guy A Rutter  1   2   3 , Anne Gresch  4 , Luis Delgadillo Silva  5 , Richard K P Benninger  6
Affiliations
Review

Exploring pancreatic beta-cell subgroups and their connectivity

Guy A Rutter et al. Nat Metab. 2024 Nov.

Erratum in

Abstract

Functional pancreatic islet beta cells are essential to ensure glucose homeostasis across species from zebrafish to humans. These cells show significant heterogeneity, and emerging studies have revealed that connectivity across a hierarchical network is required for normal insulin release. Here, we discuss current thinking and areas of debate around intra-islet connectivity, cellular hierarchies and potential "controlling" beta-cell populations. We focus on methodologies, including comparisons of different cell preparations as well as in vitro and in vivo approaches to imaging and controlling the activity of human and rodent islet preparations. We also discuss the analytical approaches that can be applied to live-cell data to identify and study critical subgroups of cells with a disproportionate role in control Ca2+ dynamics and thus insulin secretion (such as "first responders", "leaders" and "hubs", as defined by Ca2+ responses to glucose stimulation). Possible mechanisms by which this hierarchy is achieved, its physiological relevance and how its loss may contribute to islet failure in diabetes mellitus are also considered. A glossary of terms and links to computational resources are provided.

PubMed Disclaimer

Conflict of interest statement

Competing interests: G.A.R. has received grant funding from, and is a consultant for, Sun Pharmaceutical Industries. This company was not involved in the conception or writing of the present manuscript. The remaining authors declare no competing interests.

Similar articles

See all similar articles

Cited by

References

    1. Litviňuková, M. et al. Cells of the adult human heart. Nature 588, 466–472 (2020). - PubMed - PMC
    1. Steiner, D. J., Kim, A., Miller, K. & Hara, M. Pancreatic islet plasticity: interspecies comparison of islet architecture and composition. Islets 2, 135–145 (2010). - PubMed
    1. Eisenbarth, G. S. Banting Lecture 2009: An unfinished journey: molecular pathogenesis to prevention of type 1A diabetes. Diabetes 59, 759–774 (2010). - PubMed - PMC
    1. Kahn, S. E., Zraika, S., Utzschneider, K. M. & Hull, R. L. The beta cell lesion in type 2 diabetes: there has to be a primary functional abnormality. Diabetologia 52, 1003–1012 (2009). - PubMed - PMC
    1. Federation, I. D. https://idf.org/news/diabetes-now-affects-one-in-10-adults-worldwide/ (2023).

LinkOut - more resources