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DIABETES

More is better: combinatorial therapy to restore β-cell function in diabetes

Nature Metabolism volume 2, pages 130–131 (2020)Cite this article

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Current pharmacological options for diabetes treatment help patients control blood glucose levels but do not reverse the decline in insulin-secreting β-cells. A new study now shows that a pharmacological combination of insulin and a GLP-1–oestrogen conjugate not only decreases daily insulin requirements but also improves β-cell function.

Insulin-secreting pancreatic β-cells are fundamental for the maintenance of glucose homeostasis1. Insulin promotes glucose uptake and utilization by peripheral tissues. As we approach the 100th anniversary of the discovery of insulin2, efforts continue in the pursuit of a definitive cure for diabetes—a disease expected to affect more than 450 million people worldwide by 2040. The hyperglycaemia associated with both type 1 (T1D) and type 2 diabetes (T2D) is essentially caused by a relative or absolute decrease in the functional β-cell mass1. Whereas in T1D, β-cell loss is usually associated with immunologically mediated mechanisms, T2D in most people manifests as a poor β-cell compensatory response to insulin resistance and/or insulin-secretory defects1. The lack of suitable techniques to measure functional β-cell numbers through non-invasive methods has led to the assumption that a major mechanism underlying the loss of β-cell mass is due to cell death3. Recent work has suggested additional mechanisms that might regulate β-cell mass during the progression of disease; for example, β-cells might lose insulin expression, and exhibit decreased levels of transcription factors and eventual loss of cell identity, function and maturation in a process also termed dedifferentiation4. Furthermore, in mouse models of T1D, specific populations of β-cells can resist and escape immunologically mediated cell death5, and increased β-cell replication before immune attack can protect against the disease6.

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Fig. 1: Summary of the steps during loss of β-cell identity, analysed by single-cell RNA-sequencing.

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Authors and Affiliations

  1. Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA

    Dario F. De Jesus & Rohit N. Kulkarni

  2. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Dario F. De Jesus & Rohit N. Kulkarni

  3. Harvard Stem Cell Institute, Harvard University, Boston, MA, USA

    Dario F. De Jesus & Rohit N. Kulkarni

Authors
  1. Dario F. De Jesus
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  2. Rohit N. Kulkarni
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Correspondence to Rohit N. Kulkarni.

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De Jesus, D.F., Kulkarni, R.N. More is better: combinatorial therapy to restore β-cell function in diabetes. Nat Metab 2, 130–131 (2020). https://doi.org/10.1038/s42255-020-0176-y

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