Neogenesis and proliferation of beta-cells induced by human betacellulin gene transduction via retrograde pancreatic duct injection of an adenovirus vector.
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.
Tokui
Yae
Y
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
Kozawa
Junji
J
Yamagata
Kazuya
K
Zhang
Jun
J
Ohmoto
Hiroshi
H
Tochino
Yoshihiro
Y
Okita
Kohei
K
Iwahashi
Hiromi
H
Namba
Mitsuyoshi
M
Shimomura
Iichiro
I
Miyagawa
Jun-ichiro
J
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*
C587851:BTC protein, human; D066259:Betacellulin; C587852:Btc protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins