Pdk1 activity controls proliferation, survival, and growth of developing pancreatic cells

Joby J. Westmoreland, Qian Wang, Mohamed Bouzaffour, Suzanne J. Baker, Beatriz Sosa-Pineda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The formation of adequate masses of endocrine and exocrine pancreatic tissues during embryogenesis is essential to ensure proper nutrition and glucose homeostasis at postnatal stages. We generated mice with pancreas-specific ablation of the 3-phosphoinositide-dependent protein kinase 1 (Pdk1) to investigate how signaling downstream of the phosphatidylinositol-3-OH kinase (PI3K) pathway controls pancreas development. Pdk1-conditional knock-out mice were born with conspicuous pancreas hypoplasia, and within a few weeks, they developed severe hyperglycemia. Our detailed characterization of the mutant embryonic pancreas also revealed distinct temporal, cell type-specific requirements of Pdk1 activity in the control of cell proliferation, cell survival, and cell size during pancreas development. These results thus uncover Pdk1 as a novel, crucial regulator of pancreatic growth during embryogenesis. In addition, we provide evidence that Pdk1 activity is required differently in mature pancreatic cell types, since compensatory proliferation and possible mTORC2 activation occurred in exocrine cells but not in β cells of the Pdk1-deficient postnatal pancreas.

Original languageEnglish (US)
Pages (from-to)285-298
Number of pages14
JournalDevelopmental Biology
Volume334
Issue number1
DOIs
StatePublished - Oct 1 2009

Keywords

  • Cell size
  • Exocrine
  • Pancreas
  • Pdk1
  • Progenitors
  • β cell

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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