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Targeting pancreatic β cells for diabetes treatment

Nature Metabolism volume 4, pages 1097–1108 (2022)Cite this article

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Abstract

Insulin is a life-saving drug for patients with type 1 diabetes; however, even today, no pharmacotherapy can prevent the loss or dysfunction of pancreatic insulin-producing β cells to stop or reverse disease progression. Thus, pancreatic β cells have been a main focus for cell-replacement and regenerative therapies as a curative treatment for diabetes. In this Review, we highlight recent advances toward the development of diabetes therapies that target β cells to enhance proliferation, redifferentiation and protection from cell death and/or enable selective killing of senescent β cells. We describe currently available therapies and their mode of action, as well as insufficiencies of glucagon-like peptide 1 (GLP-1) and insulin therapies. We discuss and summarize data collected over the last decades that support the notion that pharmacological targeting of β cell insulin signalling might protect and/or regenerate β cells as an improved treatment of patients with diabetes.

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Fig. 1: Comparative islet architecture overview of mice versus human under healthy and diabetic states.
Fig. 2: Effects of alterations in β cell insulin signalling pathway components on β cell function.
Fig. 3: Targeting inceptor to improve β cell insulin signalling as a potential diabetes therapy.
Fig. 4: Targeting β cells to lower hyperglycaemia.

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Author notes

  1. Chirag Jain

    Present address: Immunology Discovery, Genentech Inc., South San Francisco, CA, USA

  2. Ansarullah

    Present address: The Jackson Laboratory, Bar Harbor, ME, USA

  3. These authors contributed equally: Chirag Jain, Ansarullah.

Authors and Affiliations

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

    Chirag Jain,  Ansarullah, Sara Bilekova & Heiko Lickert

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

    Chirag Jain,  Ansarullah, Sara Bilekova & Heiko Lickert

  3. Chair of β-Cell Biology, Technische Universität München, School of Medicine, Klinikum Rechts der Isar, München, Germany

    Heiko Lickert

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C.J., A., S.B. and H.L. conceived the concepts described in this review. C.J., A., S.B. and H.L. wrote the manuscript. Figures were prepared by C.J., A. and S.B.

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Correspondence to Heiko Lickert.

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The authors declare no competing interest. C.J. works as a fulltime employee at Genentech Inc., CA 94080, USA, and A. works as a fulltime employee at The Jackson Laboratory, Bar Harbor, ME 04609, USA.

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Jain, C., Ansarullah, Bilekova, S. et al. Targeting pancreatic β cells for diabetes treatment. Nat Metab 4, 1097–1108 (2022). https://doi.org/10.1038/s42255-022-00618-5

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