Open AccessPAK1 limits the expression of the pro‐apoptotic protein Bad in pancreatic islet β‐cells
Author(s) -
Wang Zhanxiang,
Thurmond Debbie C.
Publication year - 2012
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1016/j.fob.2012.09.001
Subject(s) - islet , pak1 , apoptosis , pancreatic islets , downregulation and upregulation , cytosol , cell , microbiology and biotechnology , biology , diabetes mellitus , cancer research , chemistry , endocrinology , signal transduction , biochemistry , gene , enzyme
Human type 2 diabetes is associated with β‐cell apoptosis, and human islets from diabetic donors are ∼80% deficient in PAK1 protein. Toward addressing linkage of PAK1 to β‐cell survival, PAK1–siRNA targeted MIN6 pancreatic β‐cells were found to exhibit increased caspase‐3 cleavage, cytosolic cytochrome‐C and the pro‐apoptotic protein Bad. PAK1 +/− heterozygous mouse islets recapitulated the upregulation of Bad protein expression, as did hyperglycemic treatment of human or mouse islets; Bad levels were exacerbated most in PAK1 +/− islets subjected to hyperglycemic stress. These data implicate PAK1 in β‐cell survival via quenching of Bad protein expression, and suggest PAK1 as potential molecular target to preserve β‐cell mass.