title: Pancreatic β-Cell Death due to Pdx-1 Deficiency Requires Multi-BH Domain Protein Bax but Not Bak.
abstract: Diabetes develops in Pdx1-haploinsufficient mice due to an increase in β-cell death leading to reduced β-cell mass and decreased insulin secretion. Knockdown of Pdx1 gene expression in mouse MIN6 insulinoma cells induced apoptotic cell death with an increase in Bax activation and knockdown of Bax reduced apoptotic β-cell death. In Pdx1 haploinsufficient mice, Bax ablation in β-cells increased β-cell mass, decreased the number of TUNEL positive cells and improved glucose tolerance after glucose challenge. These changes were not observed with Bak ablation in Pdx1-haploinsufficient mice. These results suggest that Bax mediates β-cell apoptosis in Pdx1-deficient diabetes.
authors.affiliation: From the Department of Medicine, University of Chicago, Chicago, Illinois 60637 and.
authors.forename: Juan
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Microbiology & Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Mao
authors.affiliation: From the Department of Medicine, University of Chicago, Chicago, Illinois 60637 and polonsky@bsd.uchicago.edu.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Polonsky
authors.affiliation: From the Department of Medicine, University of Chicago, Chicago, Illinois 60637 and decheng@uchicago.edu.
authors.forename: De-Cheng
authors.initials: DC
authors.lastname: Ren
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D018398:Homeodomain Proteins; D015534:Trans-Activators; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C084010:pancreatic and duodenal homeobox 1 protein
keywords: Bax; apoptosis; beta cell (β-cell); cell death; diabetes