Pancreatic α Cells are Resistant to Metabolic Stress-induced Apoptosis in Type 2 Diabetes

Abstract

Pancreatic α cells are exposed to metabolic stress during the evolution of type 2 diabetes (T2D), but it remains unclear whether this affects their survival. We used electron microscopy to search for markers of apoptosis and endoplasmic reticulum (ER) stress in α and β cells in islets from T2D or non-diabetic individuals. There was a significant increase in apoptotic β cells (from 0.4% in control to 6.0% in T2D), but no α cell apoptosis. We observed, however, similar ER stress in α and β cells from T2D patients. Human islets or fluorescence-activated cell sorting (FACS)-purified rat β and α cells exposed in vitro to the saturated free fatty acid palmitate showed a similar response as the T2D islets, i.e. both cell types showed signs of ER stress but only β cells progressed to apoptosis. Mechanistic experiments indicate that this α cell resistance to palmitate-induced apoptosis is explained, at least in part, by abundant expression of the anti-apoptotic protein Bcl2l1 (also known as Bcl-xL).

DOI: 10.1016/j.ebiom.2015.03.012

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@inproceedings{Marroqu2015PancreaticC, title={Pancreatic α Cells are Resistant to Metabolic Stress-induced Apoptosis in Type 2 Diabetes}, author={Laura Marroqu{\'i} and Matilde Masini and Beatriz Merino and Fabio Arturo Grieco and Isabelle Millard and Christine Dubois and Iv{\'a}n Quesada and Piero Marchetti and Miriam Cnop and Decio L. Eizirik}, booktitle={EBioMedicine}, year={2015} }