Browsing by Subject "Mouse islet"

Now showing 1 - 2 of 2
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    Depletion of PAK1 enhances Ubiquitin-mediated Survivin degradation in pancreatic β-cells
    (Taylor & Francis, 2013) Chen, Yi-Chun; Fueger, Patrick T.; Wang, Zhanxiang; Cellular and Integrative Physiology, School of Medicine
    Functional β-cell mass deficiency in diabetes results from imbalanced β-cell death and replication, and decreased PAK1 protein levels in human islets from donors with type 2 diabetes implicates a possible role for PAK1 in maintaining β-cell mass. Here, we aim to address the linkage between PAK1 and Survivin, a protein essential for β-cell replication. PAK1 knockout (KO) mouse islets exhibited decreased expression of Survivin protein. MIN6 β-cells with siRNA-mediated suppression of PAK1 also had decreased Survivin protein and exhibited an increased level of ubiquitinated-Survivin. However, no significant changes in Survivin mRNA were found in islets from PAK1 KO mice and PAK1-depleted MIN6 β-cells. The decreased Survivin level in MIN6 cells subjected to hyperglycemic stress was prevented by expression of exogenous PAK1. Moreover, overexpressing Survivin restored proliferation of β-cells that was impaired by the loss of PAK1. These data implicate a role for PAK1 in regulating Survivin protein stability in the β-cell and suggest PAK1 as a potential molecular target for the restoration of β-cell mass.
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    PAK1 limits the expression of the pro-apoptotic protein Bad in pancreatic islet β-cells
    (Elsevier, 2012-09-08) Wang, Zhanxiang; Thurmond, Debbie C.; Pediatrics, School of Medicine
    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.