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      Islet cells in human type 1 diabetes: from recent advances to novel therapies – a symposium-based roadmap for future research

      review-article
      1 , , 2 , 3 , 4 , the JDRF-DiabetesUK-INNODIA-nPOD Stockholm Symposium 2022
      The Journal of Endocrinology
      Bioscientifica Ltd
      islet, pancreas, insulin secretion, autoimmune, diabetes

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          Abstract

          There is a growing understanding that the early phases of type 1 diabetes (T1D) are characterised by a deleterious dialogue between the pancreatic beta cells and the immune system. This, combined with the urgent need to better translate this growing knowledge into novel therapies, provided the background for the JDRF–DiabetesUK–INNODIA–nPOD symposium entitled ‘Islet cells in human T1D: from recent advances to novel therapies’, which took place in Stockholm, Sweden, in September 2022. We provide in this article an overview of the main themes addressed in the symposium, pointing to both promising conclusions and key unmet needs that remain to be addressed in order to achieve better approaches to prevent or reverse T1D.

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          Most cited references128

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          Generation of functional human pancreatic β cells in vitro.

          The generation of insulin-producing pancreatic β cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation therapy in diabetes. However, insulin-producing cells previously generated from human pluripotent stem cells (hPSC) lack many functional characteristics of bona fide β cells. Here, we report a scalable differentiation protocol that can generate hundreds of millions of glucose-responsive β cells from hPSC in vitro. These stem-cell-derived β cells (SC-β) express markers found in mature β cells, flux Ca(2+) in response to glucose, package insulin into secretory granules, and secrete quantities of insulin comparable to adult β cells in response to multiple sequential glucose challenges in vitro. Furthermore, these cells secrete human insulin into the serum of mice shortly after transplantation in a glucose-regulated manner, and transplantation of these cells ameliorates hyperglycemia in diabetic mice. Copyright © 2014 Elsevier Inc. All rights reserved.
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            An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes

            Type 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed.
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              Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure

              Loss of functional β-cell mass is the key mechanism leading to the two main forms of diabetes mellitus - type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Understanding the mechanisms behind β-cell failure is critical to prevent or revert disease. Basic pathogenic differences exist in the two forms of diabetes mellitus; T1DM is immune mediated and T2DM is mediated by metabolic mechanisms. These mechanisms differentially affect early β-cell dysfunction and eventual fate. Over the past decade, major advances have been made in the field, mostly delivered by studies on β-cells in human disease. These advances include studies of islet morphology and human β-cell gene expression in T1DM and T2DM, the identification and characterization of the role of T1DM and T2DM candidate genes at the β-cell level and the endoplasmic reticulum stress signalling that contributes to β-cell failure in T1DM (mostly IRE1 driven) and T2DM (mostly PERK-eIF2α dependent). Here, we review these new findings, focusing on studies performed on human β-cells or on samples obtained from patients with diabetes mellitus.

                Author and article information

                Journal
                J Endocrinol
                J Endocrinol
                JOE
                The Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                0022-0795
                1479-6805
                31 August 2023
                26 July 2023
                01 September 2023
                : 259
                : 1
                : e230082
                Affiliations
                [1 ]School of Medicine , University of Dundee, Dundee, United Kingdom of Great Britain and Northern Ireland
                [2 ]ULB Center for Diabetes Research , Université Libre de Bruxelles Faculté de Médecine, Bruxelles, Belgium
                [3 ]JDRF International , New York, NY, USA
                [4 ]Cardiff University School of Medicine , Cardiff, United Kingdom of Great Britain and Northern Ireland
                Author notes
                Correspondence should be addressed to J Cantley: JCantley001@ 123456dundee.ac.uk
                Author information
                http://orcid.org/0000-0003-2509-1271
                Article
                JOE-23-0082
                10.1530/JOE-23-0082
                10502961
                37493471
                19bdbdff-2039-4abd-9f0d-413253d780e0
                © the author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 21 March 2023
                : 31 August 2023
                Categories
                Review

                Endocrinology & Diabetes
                islet,pancreas,insulin secretion,autoimmune,diabetes
                Endocrinology & Diabetes
                islet, pancreas, insulin secretion, autoimmune, diabetes

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