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

Pancreatic a 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 alpha and beta cells in islets from T2D or non-diabetic individuals. There was a significant increase in apoptotic beta cells (from 0.4% in control to 6.0% in T2D), but no alpha cell apoptosis. We observed, however, similar ER stress in alpha and beta cells from T2D patients. Human islets or fluorescence-activated cell sorting (FACS)-purified rat beta and alpha 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 beta cells progressed to apoptosis. Mechanistic experiments indicate that this a 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). (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).