New-found brake calibrates insulin action in β-cells

Kulkarni, Rohit N.

doi:10.1038/d41586-021-00141-9

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27 January 2021

New-found brake calibrates insulin action in β-cells

Insulin is produced by pancreatic β-cells. The identification of a regulator of insulin signalling in these cells cements the long-standing idea that this pathway has a key role in β-cell biology.

Rohit N. Kulkarni⁰

Rohit N. Kulkarni
1. Rohit N. Kulkarni is at the Joslin Diabetes Center, Boston, the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, and the Harvard Stem Cell Institute, Boston, Massachusetts 02215, USA.
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It is almost a century since insulin was first used to treat diabetes¹. Since then, a great deal has been learnt about the complex metabolic pathways that are regulated by insulin and the related molecule insulin-like growth factor 1 (IGF1), acting through receptor proteins (reviewed in ref. 2)². But it is less clear how the activity of these receptors is regulated in the cells that actually produce insulin, the pancreatic β-cells. Such knowledge is urgently needed because reduced β-cell function is a key contributor to diabetes. Deciphering the molecular pathways that regulate β-cells might therefore help to better manage, or even prevent, this disease. Writing in Nature, Ansarullah et al.³ identify a previously unknown regulator of β-cells, and outline the mechanism by which this protein can ‘tailor’ expression of the insulin receptor.

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Nature 590, 221-223 (2021)

doi: https://doi.org/10.1038/d41586-021-00141-9

References

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[1] Banting, F. G., Best, C. H., Collip, J. B., Campbell, W. R. & Fletcher, A. A. Can. Med. Assoc. J. 12, 141–146 (1922).
PubMed Google Scholar

[2] Stewart, A. F. et al. Diabetes 64, 1872–1885 (2015).
Article PubMed Google Scholar

[3] Ansarullah et al. Nature 590, 326–331 (2021).
Article Google Scholar

[4] Xu, G. G. & Rothenberg, P. L. Diabetes 47, 1243–1252 (1998).
Article PubMed Google Scholar

[5] Kulkarni, R. N. et al. Cell 96, 329–339 (1999).
Article PubMed Google Scholar

[6] Otani, K. et al. Am. J. Physiol. Endocrinol. Metab. 286, E41–E49 (2004).
Article PubMed Google Scholar

[7] Leibiger, I. B., Leibiger, B., Moede, T. & Berggren, P. O. Mol. Cell 1, 933–938 (1998).
Article PubMed Google Scholar

[8] Aspinwall, C. A., Lakey, J. R. T. & Kennedy, R. T. J. Biol. Chem. 274, 6360–6365 (1999).
Article PubMed Google Scholar

[9] Johnson, J. D. & Misler, S. Proc. Natl Acad. Sci. USA 99, 14566–14571 (2002).
Article PubMed Google Scholar

[10] da Silva Xavier, G., Qian, Q., Cullen, P. J. & Rutter, G. A. Biochem. J. 377, 149–158 (2004).
Article PubMed Google Scholar

[11] Ohsugi, M. et al. J. Biol. Chem. 280, 4992–5003 (2005).
Article PubMed Google Scholar

[12] Withers, D. J. et al. Nature 391, 900–904 (1998).
Article PubMed Google Scholar

[13] Tuttle, R. L. et al. Nature Med. 7, 1133–1137 (2001).
Article PubMed Google Scholar

[14] Xuan, S. et al. J. Clin. Invest. 110, 1011–1019 (2002).
Article PubMed Google Scholar

[15] Kulkarni, R. N. et al. Nature Genet. 31, 111–115 (2002).
Article PubMed Google Scholar

[16] Halperin, F. et al. Diabetes 61, 301–309 (2012).
Article PubMed Google Scholar

[17] Mari, A. et al. Diabetes 60, 3141–3147 (2011).
Article PubMed Google Scholar

[18] Hancock, M. L. et al. Cell 177, 722–736 (2019).
Article PubMed Google Scholar

[19] Shirakawa, J. et al. Cell Metab. 25, 868–882 (2017).
Article PubMed Google Scholar

[20] De Jesus, D. F. et al. Nature Metab. 1, 765–774 (2019).
Article PubMed Google Scholar

New-found brake calibrates insulin action in β-cells

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