Regulation of pancreatic duct cell differentiation by phosphatidylinositol-3 kinase

Hiroaki Watanabe, Hiroshi Saito, Junji Ueda, B. Mark Evers

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

We have previously demonstrated that the phosphatidylinositol-3 kinase (PI3K)/Akt signaling is essential for pancreatic regeneration after partial pancreatectomy in mice. In the present study, we examined a role of PI3K/Akt signaling for pancreatic duct cell differentiation into insulin-producing cells. Epithelial-like cells were isolated from mouse pancreas and confirmed to be positive for a duct cell marker cytokeratin-20 (CK-20) but negative for insulin. Incubation of these cells with epidermal growth factor, exhibited a gradual increase in Akt phosphorylation and expression of pancreatic duodenal homeobox-1 (PDX-1), a regulator of β-cell differentiation. Three weeks later, these CK-20-positive cells were noted to express insulin as determined by immunofluorescent double-staining. Akt phosphorylation, PDX-1 expression, and insulin production were effectively reduced by blocking the PI3K/Akt pathway using siRNA to the p85α regulatory subunit of PI3K. Our results demonstrate that PI3K/Akt activation has a critical role for pancreatic duct cell differentiation into insulin-producing cells.

Original languageEnglish
Pages (from-to)33-37
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume370
Issue number1
DOIs
StatePublished - May 23 2008

Bibliographical note

Funding Information:
We thank Ms. Karen Martin for manuscript preparation and Mr. Tatsuo Uchida statistical analysis. This work was supported from Grants from P01DK35608, R37AG10885, R01DK48498, and R01AG025273 from the National Institutes of Health.

Keywords

  • Duct differentiation
  • Insulin
  • PDX-1
  • PI3K
  • Pancreatic regeneration
  • Wortmannin
  • siRNA
  • β-Cell differentiation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Regulation of pancreatic duct cell differentiation by phosphatidylinositol-3 kinase'. Together they form a unique fingerprint.

Cite this