Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Year in Review
  • Published:

ISLET BIOLOGY IN 2021

New insights into β-cell failure, regeneration and replacement

Nature Reviews Endocrinology volume 18, pages 79–80 (2022)Cite this article

Subjects

In 2021, several discoveries shed light on the pathomechanisms of β-cell failure during the initiation and progression of diabetes mellitus, and validated novel molecular targets for intervention. Moreover, the field of stem-cell-derived replacements for β-cells is rapidly advancing. These advances bring us closer to therapies to protect and/or regenerate β-cell mass.

Key advances

  • Single-cell epigenomics and genome-wide association studies (GWAS) of type 1 diabetes mellitus (T1DM) detected enrichment of risk variants in cis-regulatory elements, implicating the contribution of pancreatic exocrine dysfunction to the development of T1DM2.

  • Combining single-cell epigenomics and GWAS of type 2 diabetes mellitus (T2DM) identified a risk variant at the KCNQ1 locus, which impacts insulin synthesis3.

  • Multi-omics analysis of samples from deeply metabolically profiled individuals uncovered molecular changes associated with β-cell pathophysiology in T2DM and identified novel lipid biomarkers4.

  • The unexpected discovery of an insulin inhibitory receptor (inceptor) provided insights into how insulin signalling and the insulin receptor are regulated in β-cells7.

  • Ready-made microvessels improved the survival and function of transplanted stem-cell-derived islets and primary human islets into mice, enhancing T1DM remission9.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Novel approaches and targets for β-cell protection, regeneration and replacement.

References

  1. Sims, E. K., Carr, A. L. J., Oram, R. A., DiMeglio, L. A. & Evans-Molina, C. 100 years of insulin: celebrating the past, present and future of diabetes therapy. Nat. Med. 27, 1154–1164 (2021).

    Article  CAS  Google Scholar 

  2. Chiou, J. et al. Interpreting type 1 diabetes risk with genetics and single-cell epigenomics. Nature 594, 398–402 (2021).

    Article  CAS  Google Scholar 

  3. Chiou, J. et al. Single-cell chromatin accessibility identifies pancreatic islet cell type- and state-specific regulatory programs of diabetes risk. Nat. Genet. 53, 455–466 (2021).

    Article  CAS  Google Scholar 

  4. Wigger, L. et al. Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories towards type 2 diabetes. Nat. Metab. 3, 1017–1031 (2021).

    Article  CAS  Google Scholar 

  5. Butler, A. E. et al. β-cell deficit in obese type 2 diabetes, a minor role of β-cell dedifferentiation and degranulation. J. Clin. Endocrinol. Metab. 101, 523–532 (2016).

    Article  CAS  Google Scholar 

  6. Cinti, F. et al. Evidence of β-cell dedifferentiation in human type 2 diabetes. J. Clin. Endocrinol. Metab. 101, 1044–1054 (2016).

    Article  CAS  Google Scholar 

  7. Ansarullah et al. Inceptor counteracts insulin signalling in β-cells to control glycaemia. Nature 590, 326–331 (2021).

    Article  CAS  Google Scholar 

  8. Ueki, K. et al. Total insulin and IGF-I resistance in pancreatic β cells causes overt diabetes. Nat. Genet. 38, 583–588 (2006).

    Article  CAS  Google Scholar 

  9. Aghazadeh, Y. et al. Microvessels support engraftment and functionality of human islets and hESC-derived pancreatic progenitors in diabetes models. Cell Stem Cell 28, 1936–1949.e8 (2021).

    Article  CAS  Google Scholar 

  10. Wang, X. et al. A nanofibrous encapsulation device for safe delivery of insulin-producing cells to treat type 1 diabetes. Sci. Transl. Med. 13, eabb4601 (2021).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany

    Mostafa Bakhti & Heiko Lickert

  2. German Center for Diabetes Research (DZD), Neuherberg, Germany

    Mostafa Bakhti & Heiko Lickert

  3. Technische Universität München, School of Medicine, Munich, Germany

    Heiko Lickert

Authors
  1. Mostafa Bakhti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heiko Lickert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heiko Lickert.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bakhti, M., Lickert, H. New insights into β-cell failure, regeneration and replacement. Nat Rev Endocrinol 18, 79–80 (2022). https://doi.org/10.1038/s41574-021-00611-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41574-021-00611-0

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing