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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/G1139    most recent 00338.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wagner, M. Articles by Schmid, R. M. PubMed PubMed Citation Articles by Wagner, M. Articles by Schmid, R. M.

HORMONES AND SIGNALING

Selective expansion of the β-cell compartment in the pancreas of keratinocyte growth factor transgenic mice

¹Department of Internal Medicine I, University Ulm; ²Herzzentrum University, Göttingen; and ³Department of Internal Medicine II, Technische Universität München

Submitted 25 July 2007 ; accepted in final form 16 March 2008

Epithelial-mesenchymal interactions are essential for growth, differentiation, and regeneration of exocrine and endocrine cells in the pancreas. The keratinocyte growth factor (KGF) is derived from mesenchyme and has been shown to promote epithelial cell differentiation and proliferation in a paracrine fashion. Here, we have examined the effect of ectopic expression of KGF on pancreatic differentiation and proliferation in transgenic mice by using the proximal elastase promoter. KGF transgenic mice were generated following standard procedures and analyzed by histology, morphometry, immunohistochemistry, Western blot analysis, and glucose tolerance testing. In KGF transgenic mice, the number of islets, the average size of islets, and the relation of endocrine to exocrine tissue are increased compared with littermate controls. An expansion of the β-cell population is responsible for the increase in the endocrine compartment. Ectopic expression of KGF results in proliferation of β-cells and pancreatic duct cells most likely through activation of the protein kinase B (PKB)/Akt signaling pathway. Glucose tolerance and insulin secretion are impaired in transgenic animals. These results provide evidence that ectopic expression of KGF in acinar cells promotes the expansion of the β-cell lineage in vivo through activation of the PKB/Akt pathway. Furthermore, the observed phenotype demonstrates that an increase in the β-cell compartment does not necessarily result in an improved glucose tolerance in vivo.

β-cell proliferation; protein kinase B; glucose tolerance