Abstract
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.