PAK1 limits the expression of the pro-apoptotic protein Bad in pancreatic islet β-cells

Zhanxiang Wang, Debbie C. Thurmond

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)273-277
Number of pages5
JournalFEBS Open Bio
Volume2
DOIs
StatePublished - Sep 18 2012

Keywords

  • Apoptosis
  • Bad
  • Human islet
  • Mouse islet
  • PAK1
  • Pancreatic β-cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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