Neogenesis and proliferation of beta-cells induced by human betacellulin gene transduction via retrograde pancreatic duct injection of an adenovirus vector |
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Authors: | Tokui Yae Kozawa Junji Yamagata Kazuya Zhang Jun Ohmoto Hiroshi Tochino Yoshihiro Okita Kohei Iwahashi Hiromi Namba Mitsuyoshi Shimomura Iichiro Miyagawa Jun-ichiro |
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Affiliation: | Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2-B5, Yamadaoka, Suita-city, Osaka 565-0871, Japan. ytokui@imed2.med.osaka-u.ac.jp |
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Abstract: | Betacellulin (BTC) has been shown to have a role in the differentiation and proliferation of beta-cells both in vitro and in vivo. We administered a human betacellulin (hBTC) adenovirus vector to male ICR mice via retrograde pancreatic duct injection. As a control, we administered a beta-galactosidase adenovirus vector. In the mice, hBTC protein was mainly overexpressed by pancreatic duct cells. On immunohistochemical analysis, we observed features of beta-cell neogenesis as newly formed insulin-positive cells in the duct cell lining or islet-like cell clusters (ICCs) closely associated with the ducts. The BrdU labeling index of beta-cells was also increased by the betacellulin vector compared with that of control mice. These results indicate that hBTC gene transduction into adult pancreatic duct cells promoted beta-cell differentiation (mainly from duct cells) and proliferation of pre-existing beta-cells, resulting in an increase of the beta-cell mass that improved glucose tolerance in diabetic mice. |
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Keywords: | Betacellulin Adenovirus Retrograde pancreatic duct injection β-Cell Differentiation Proliferation BrdU labeling index Duct cells β-Cell mass Glucose tolerance |
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