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.

Metabolism

Waxy lipids and waning insulin secretion

Nature Cell Biology volume 25, pages 7–8 (2023)Cite this article

Subjects

In type 2 diabetes, altered lipid metabolism causes a defect in insulin secretion. A study now shows how reduced very long-chain sphingolipids in β cells may impair the export of insulin-processing enzymes from the endoplasmic reticulum. The resulting defect in insulin production causes increased blood glucose concentrations.

In 2021, the International Diabetes Federation estimated that there were 537 million adults living with diabetes, accounting for 1 in 10 individuals worldwide. More than 90% of these individuals have type 2 diabetes, which occurs in the setting of obesity and increased age. Diabetes puts people at risk of debilitating and life-threatening complications, and results in an enormous burden of healthcare costs. Although diabetes is diagnosed on the basis of increased blood glucose concentrations, the root causes are multifactorial. In type 2 diabetes, excess lipids are present in the circulation and in tissues, and toxic effects of these lipids — known as lipotoxicity — is thought to drive cellular dysfunction. Diacylglycerols, cholesterol esters and sphingolipids have all been implicated in causing effects in various tissues that, combined, lead to the clinical manifestations of diabetes1,2. A challenge is to understand precisely how these lipids act. What lipid is responsible for what cellular dysfunction, in which particular cell type?

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

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

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

Fig. 1: Diabetes-associated lipotoxicity in pancreatic β cells may be characterized by a selective reduction in specific VLSL species, which results in impaired processing of proinsulin to produce insulin.

References

  1. Roden, M. & Shulman, G. I. Nature 576, 51–60 (2019).

    Article  CAS  Google Scholar 

  2. Nicholson, R. J., Norris, M. K., Poss, A. M., Holland, W. L. & Summers, S. A. Annu. Rev. Nutr. 42, 115–144 (2022).

    Article  Google Scholar 

  3. Halban, P. A. et al. Diabetes Care 37, 1751–1758 (2014).

    Article  Google Scholar 

  4. Vasiljevic, J., Torkko, J. M., Knoch, K. P. & Solimena, M. Diabetologia 63, 1981–1989 (2020).

    Article  Google Scholar 

  5. Ramzy, A., Asadi, A. & Kieffer, T. J. Diabetes 69, 1451–1462 (2020).

    Article  Google Scholar 

  6. Parchure, A. et al. J. Cell Biol. 221, e202206132 (2022).

    Article  CAS  Google Scholar 

  7. Henquin, J. C. Mol. Metab. 30, 230–239 (2019).

    Article  CAS  Google Scholar 

  8. Griess, K. et al. Nat. Cell Biol. https://doi.org/10.1038/s41556-022-01027-2 (2022).

  9. Stijnen, P., Ramos-Molina, B., O’Rahilly, S. & Creemers, J. W. Endocr. Rev. 37, 347–371 (2016).

    Article  CAS  Google Scholar 

  10. Contreras, F. X. et al. Nature 481, 525–529 (2012).

    Article  CAS  Google Scholar 

  11. Anwar, M. U. et al. Dev. Cell 57, 2334–2346 e2338 (2022).

    Article  CAS  Google Scholar 

  12. Jayashankar, V. et al. EMBO Mol. Med. 13, e13086 (2021).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA

    Jonathan S. Bogan

  2. Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA

    Jonathan S. Bogan

  3. Yale Center for Molecular and Systems Metabolism, Yale School of Medicine, New Haven, CT, USA

    Jonathan S. Bogan

Authors
  1. Jonathan S. Bogan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan S. Bogan.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bogan, J.S. Waxy lipids and waning insulin secretion. Nat Cell Biol 25, 7–8 (2023). https://doi.org/10.1038/s41556-022-01036-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41556-022-01036-1

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