title: 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).
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
authors.forename: Laura
authors.initials: L
authors.lastname: Marroqui
authors.affiliation: Department of Clinical and Experimental Medicine, Pancreatic Islet Cell Laboratory, University of Pisa, Pisa 56126, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Masini
authors.affiliation: Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM) Instituto de Bioingeniería, Universidad Miguel Hernández, 03202 Elche, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Merino
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Grieco
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Millard
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Dubois
authors.affiliation: Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM) Instituto de Bioingeniería, Universidad Miguel Hernández, 03202 Elche, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Quesada
authors.affiliation: Department of Clinical and Experimental Medicine, Pancreatic Islet Cell Laboratory, University of Pisa, Pisa 56126, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: 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.
authors.forename: Miriam
authors.initials: M
authors.lastname: Cnop
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
authors.forename: Decio L
authors.initials: DL
authors.lastname: Eizirik
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D050416:Glucagon-Secreting Cells / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology / Q000648:ultrastructure; D008055:Lipids / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D019308:Palmitic Acid / Q000494:pharmacology; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000187:drug effects; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008055:Lipids; D051020:bcl-X Protein; D019308:Palmitic Acid
keywords: Apoptosis; Bcl2l1; ER stress; Metabolic stress; Palmitate; Pancreatic α cells; Type 2 diabetes