%0 Journal Article %T Dysfunction of Persisting β Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis %V 31 %N 1 %P 107469 %U http://www.sciencedirect.com/science/article/pii/S2211124720303478 %X 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. %G en %J Cell Reports %A Cohrs, Christian M. %A Panzer, Julia K. %A Drotar, Denise M. %A Enos, Stephen J. %A Kipke, Nicole %A Chen, Chunguang %A Bozsak, Robert %A Schöniger, Eyke %A Ehehalt, Florian %A Distler, Marius %A Brennand, Ana %A Bornstein, Stefan R. %A Weitz, Jürgen %A Solimena, Michele %A Speier, Stephan %D April 7, 2020 %K Type 2 diabetes WP5 beta cell function beta cell mass human pancreas insulin secretion