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EBioMedicine. 2015 Mar 17;2(5):378-85. doi: 10.1016/j.ebiom.2015.03.012. eCollection 2015 May.

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

Author information

1
ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
2
Department of Clinical and Experimental Medicine, Pancreatic Islet Cell Laboratory, University of Pisa, Pisa 56126, Italy.
3
Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM) Instituto de Bioingeniería, Universidad Miguel Hernández, 03202 Elche, Spain.
4
ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium ; Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.

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).

KEYWORDS:

Apoptosis; Bcl2l1; ER stress; Metabolic stress; Palmitate; Pancreatic α cells; Type 2 diabetes

PMID:
26137583
PMCID:
PMC4485913
DOI:
10.1016/j.ebiom.2015.03.012
[Indexed for MEDLINE]
Free PMC Article

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