Dysfunction of Persisting β Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis

doi:10.1016/j.celrep.2020.03.033

. 2020 Apr 7;31(1):107469.

doi: 10.1016/j.celrep.2020.03.033.

Dysfunction of Persisting β Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis

Affiliations

¹ Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; Institute of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
² German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Molecular Diabetology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
³ Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Molecular Diabetology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
⁴ Department of GI-, Thoracic- and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁵ Department of Diabetes, School of Life Science & Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK.
⁶ Department of Diabetes, School of Life Science & Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK; Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany.
⁷ Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; Department of GI-, Thoracic- and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁸ Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Molecular Diabetology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
⁹ Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; Institute of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany. Electronic address: stephan.speier@tu-dresden.de.

PMID: 32268101
DOI: 10.1016/j.celrep.2020.03.033

Free article

Dysfunction of Persisting β Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis

Christian M Cohrs et al. Cell Rep. 2020.

Free article

. 2020 Apr 7;31(1):107469.

doi: 10.1016/j.celrep.2020.03.033.

Authors

Affiliations

¹ Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; Institute of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
² German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Molecular Diabetology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
³ Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Molecular Diabetology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
⁴ Department of GI-, Thoracic- and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁵ Department of Diabetes, School of Life Science & Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK.
⁶ Department of Diabetes, School of Life Science & Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK; Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany.
⁷ Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; Department of GI-, Thoracic- and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁸ Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Molecular Diabetology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
⁹ Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; Institute of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany. Electronic address: stephan.speier@tu-dresden.de.

PMID: 32268101
DOI: 10.1016/j.celrep.2020.03.033

Abstract

Type 2 diabetes is characterized by peripheral insulin resistance and insufficient insulin release from pancreatic islet β cells. However, the role and sequence of β cell dysfunction and mass loss for reduced insulin levels in type 2 diabetes pathogenesis are unclear. Here, we exploit freshly explanted pancreas specimens from metabolically phenotyped surgical patients using an in situ tissue slice technology. This approach allows assessment of β cell volume and function within pancreas samples of metabolically stratified individuals. We show that, in tissue of pre-diabetic, impaired glucose-tolerant subjects, β cell volume is unchanged, but function significantly deteriorates, exhibiting increased basal release and loss of first-phase insulin secretion. In individuals with type 2 diabetes, function within the sustained β cell volume further declines. These results indicate that dysfunction of persisting β cells is a key factor in the early development and progression of type 2 diabetes, representing a major target for diabetes prevention and therapy.

Keywords: Type 2 diabetes; beta cell function; beta cell mass; human pancreas; insulin secretion.

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Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

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Dysfunction of Persisting β Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis

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Dysfunction of Persisting β Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis

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