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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:73294 |
| Date | 18 January 2021 |
| Creators | Cohrs, Christian M., Panzer, Julia K., Drotar, Denise M., Enos, Stephen J., Kipke, Nicole, Chen, Chunguang, Bozsak, Robert, Schöniger, Eyke, Ehehalt, Florian, Distler, Marius, Brennand, Ana, Bornstein, Stefan R., Weitz, Jürgen, Solimena, Michele, Speier, Stephan |
| Publisher | Elsevier |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2211-1247, 107469, 2211-1247, 10.1016/j.celrep.2020.03.033, info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/GRK 2251/288034826//Immunological and Cellular Strategies in Metabolic Disease/ICSMD, info:eu-repo/grantAgreement/European Commission/FP7 | SP1 | SP1-JTI/115005//Improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in diabetes/IMIDIA, info:eu-repo/grantAgreement/European Commission/H2020 | IMI2-RIA/115881//Assessing risk and progression of prediabetes and type 2 diabetes to enable disease modification/RHAPSODY, info:eu-repo/grantAgreement/European Commission/H2020 | IMI2-RIA/115797//Translational approaches to disease modifying therapy of type 1 diabetes: an innovative approach towards understanding and arresting type 1 diabetes/INNODIA |
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