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.

DIABETES

A multi-omics roadmap of β-cell failure in type 2 diabetes mellitus

Pancreatic β-cell dysfunction contributes to type 2 diabetes mellitus (T2DM) pathogenesis. However, human islet studies have revealed few consistent molecular changes in T2DM, owing partly to technical and biological confounding factors. A new multi-omics study of islets from well-phenotyped living donors attempts to overcome these limitations to catalogue T2DM-associated molecular changes.

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

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Relationships between islet gene and protein expression, plasma lipids and plasma HbA1c levels.

References

  1. Hudish, L. I., Reusch, J. E. & Sussel, L. β Cell dysfunction during progression of metabolic syndrome to type 2 diabetes. J. Clin. Invest. 129, 4001–4008 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  2. 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  PubMed  Google Scholar 

  3. Solimena, M. et al. Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes. Diabetologia 61, 641–657 (2018).

    Article  CAS  PubMed  Google Scholar 

  4. Wortham, M. et al. Integrated in vivo quantitative proteomics and nutrient tracing reveals age-related metabolic rewiring of pancreatic β cell function. Cell Rep. 25, 2904–2918 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Doliba, N. M. et al. Glucokinase activation repairs defective bioenergetics of islets of Langerhans isolated from type 2 diabetics. Am. J. Physiol. Endocrinol. Metab. 302, E87–E102 (2012).

    Article  CAS  PubMed  Google Scholar 

  6. Wang, Y. J. et al. Single-cell transcriptomics of the human endocrine pancreas. Diabetes 65, 3028–3038 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Lawlor, N. et al. Single-cell transcriptomes identify human islet cell signatures and reveal cell-type-specific expression changes in type 2 diabetes. Genome Res. 27, 208–222 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Benninger, R. K. P. & Hodson, D. J. New understanding of β-cell heterogeneity and in situ islet function. Diabetes 67, 537–547 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank M. Wortham and H. Zhu for comments. Work in the Sander laboratory is supported by grants from the National Institutes of Health R01DK078803, R01DK068471, R01DK114427, R01DK122607, U01DK120429 and UG3DK122639.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maike Sander.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wang, G., Sander, M. A multi-omics roadmap of β-cell failure in type 2 diabetes mellitus. Nat Rev Endocrinol 17, 641–642 (2021). https://doi.org/10.1038/s41574-021-00556-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41574-021-00556-4

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