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

Joby J Westmoreland1, Qian Wang, Mohamed Bouzaffour

  • 1Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Developmental Biology
|July 29, 2009
PubMed

Insights

3-phosphoinositide-dependent protein kinase 1 (Pdk1) is crucial for embryonic pancreas development and glucose homeostasis. Its ablation causes pancreas hypoplasia and severe hyperglycemia in mice.

Area of Science:

  • Developmental Biology
  • Endocrinology
  • Molecular Biology

Background:

  • Pancreatic development is critical for lifelong metabolic health.
  • The phosphatidylinositol-3-OH kinase (PI3K) signaling pathway regulates cell growth and survival.
  • The role of Pdk1 in pancreas organogenesis is not well understood.

Purpose of the Study:

  • To investigate the role of Pdk1 in pancreas development.
  • To determine how PI3K signaling downstream of Pdk1 controls pancreatic growth.
  • To elucidate the cell type-specific functions of Pdk1 in the developing and mature pancreas.

Main Methods:

  • Generation of pancreas-specific Pdk1 conditional knock-out mice.
  • Histological analysis of embryonic and postnatal pancreas.
  • Assessment of glucose homeostasis and hyperglycemia.
  • Evaluation of cell proliferation, survival, and size.

Main Results:

  • Pdk1 ablation resulted in significant pancreas hypoplasia and severe hyperglycemia.
  • Pdk1 is essential for embryonic pancreatic cell proliferation, survival, and size.
  • Distinct temporal and cell type-specific requirements for Pdk1 were observed.
  • Mature exocrine cells showed compensatory proliferation and potential mTORC2 activation, unlike beta cells.

Conclusions:

  • Pdk1 is a critical regulator of pancreatic growth during embryogenesis.
  • Pdk1 signaling is indispensable for maintaining glucose homeostasis postnatally.
  • Differential Pdk1 activity is required in distinct pancreatic cell types for proper function.

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