Journal
NATURE REVIEWS ENDOCRINOLOGY
Volume 16, Issue 7, Pages 349-362Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41574-020-0355-7
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Funding
- Welbio-FNRS (Fonds National de la Recherche Scientifique), Belgium
- Dutch Diabetes Fonds (DDFR), Holland
- Indiana Biosciences Research Institute (IBRI), Indianapolis, Indiana, USA
- European Union's Horizon 2020 research and innovation programme, project T2DSystems [667191]
- Brussels Capital Region-Innoviris project Diatype
- Innovative Medicines Initiative 2 Joint Undertaking - European Union's Horizon 2020 research and innovation programme [115797]
- EFPIA
- JDRF
- Leona M. and Harry B. Helmsley Charitable Trust
- Innovative Medicines Initiative 2 Joint Undertaking Rhapsody - European Union's Horizon 2020 Research and Innovation Programme [115881]
- Swiss State Secretariat for Education, Research and Innovation (SERI) [16.0097]
- FNRS, Belgium
- Spanish Ministry of Economy and Competitiveness [SAF2017-86242-R]
- Marato TV3 [201624.10]
- EFSD/JDRF/Lilly Programme on Type 1 Diabetes Research
- ISCIII [PIE16/00011]
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Loss of functional beta-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 beta-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 beta-cell dysfunction and eventual fate. Over the past decade, major advances have been made in the field, mostly delivered by studies on beta-cells in human disease. These advances include studies of islet morphology and human beta-cell gene expression in T1DM and T2DM, the identification and characterization of the role of T1DM and T2DM candidate genes at the beta-cell level and the endoplasmic reticulum stress signalling that contributes to beta-cell failure in T1DM (mostly IRE1 driven) and T2DM (mostly PERK-eIF2 alpha dependent). Here, we review these new findings, focusing on studies performed on human beta-cells or on samples obtained from patients with diabetes mellitus. Understanding the mechanisms behind beta-cell failure in diabetes mellitus is critical to prevent or revert disease. This Review highlights new findings from studies performed on human beta-cells or on samples obtained from patients with type 1 or type 2 diabetes mellitus.
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