Regulation of pancreatic duct cell differentiation by phosphatidylinositol-3 kinase |
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Authors: | Watanabe Hiroaki Saito Hiroshi Ueda Junji Evers B Mark |
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Institution: | a Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0536, USA b Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX 77555, USA c Sealy Center for Cancer Cell Biology, The University of Texas Medical Branch, Galveston, TX 77555, USA |
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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. |
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Keywords: | PDX-1 PI3K Insulin Pancreatic regeneration Duct differentiation β-Cell differentiation Wortmannin siRNA |
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