title: Neogenesis and proliferation of beta-cells induced by human betacellulin gene transduction via retrograde pancreatic duct injection of an adenovirus vector.
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.
authors.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
authors.forename: Yae
authors.initials: Y
authors.lastname: Tokui
authors.forename: Junji
authors.initials: J
authors.lastname: Kozawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohmoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tochino
authors.forename: Kohei
authors.initials: K
authors.lastname: Okita
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwahashi
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Namba
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Miyagawa
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D066259:Betacellulin; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008845:Microinjections; D010183:Pancreatic Ducts / Q000166:cytology / Q000502:physiology; D014161:Transduction, Genetic / Q000379:methods*
chemical_list: C587851:BTC protein, human; D066259:Betacellulin; C587852:Btc protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins