TY - JOUR
T1 - Reversal of streptozotocin-induced hyperglycemia by continuous supply of betacellulin in mice
AU - Yamamoto, Yoritsuna
AU - Yamada, Satoko
AU - Kodera, Tsutomu
AU - Hara, Akemi
AU - Motoyoshi, Kazuo
AU - Tanaka, Yuji
AU - Nagaoka, Tadahiro
AU - Seno, Masaharu
AU - Kojima, Itaru
N1 - Funding Information:
The present study was supported by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan and a Grant-in-Aid from the Realization of Regenerative Medicine. The authors are grateful to Mayumi Odagiri for secretarial assistance.
PY - 2008
Y1 - 2008
N2 - Previous studies have shown the efficacy of betacellulin (BTC) to promote β-cell regeneration. Because of its short half-life, however, the effect of BTC may have been underestimated. This study was conducted to assess the effect of continuous administration of BTC on β-cell regeneration. Adenovirus vectors encoding proBTC (Ad-proBTC) and mature BTC (Ad-mBTC) were prepared, and the efficacy of secretion of BTC was compared in AML12 hepatocytes. When AML12 cells were infected with Ad-proBTC or Ad-mBTC, cells infected with Ad-mBTC secreted considerably larger amount of BTC. We then infused Ad-mBTC into the mouse tail vein. Expression of BTC was detected in the liver for at least 21 days, and serum BTC was maintained at approximately 1 ng/ml for 7 days. When Ad-mBTC was infused immediately after administration of STZ (170 mg/kg), elevation of the plasma glucose induced by STZ was markedly inhibited, and the plasma glucose concentration remained at less than 200 mg/dl for 21 days. The insulin content and the β-cell mass were significantly increased in Ad-mBTC-infused mice. These results indicate that continuous administration of BTC is quite effective in promoting regeneration of β-cells.
AB - Previous studies have shown the efficacy of betacellulin (BTC) to promote β-cell regeneration. Because of its short half-life, however, the effect of BTC may have been underestimated. This study was conducted to assess the effect of continuous administration of BTC on β-cell regeneration. Adenovirus vectors encoding proBTC (Ad-proBTC) and mature BTC (Ad-mBTC) were prepared, and the efficacy of secretion of BTC was compared in AML12 hepatocytes. When AML12 cells were infected with Ad-proBTC or Ad-mBTC, cells infected with Ad-mBTC secreted considerably larger amount of BTC. We then infused Ad-mBTC into the mouse tail vein. Expression of BTC was detected in the liver for at least 21 days, and serum BTC was maintained at approximately 1 ng/ml for 7 days. When Ad-mBTC was infused immediately after administration of STZ (170 mg/kg), elevation of the plasma glucose induced by STZ was markedly inhibited, and the plasma glucose concentration remained at less than 200 mg/dl for 21 days. The insulin content and the β-cell mass were significantly increased in Ad-mBTC-infused mice. These results indicate that continuous administration of BTC is quite effective in promoting regeneration of β-cells.
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U2 - 10.1080/08977190802136854
DO - 10.1080/08977190802136854
M3 - Article
C2 - 19378417
AN - SCOPUS:59749091538
SN - 0897-7194
VL - 26
SP - 173
EP - 179
JO - Growth Factors
JF - Growth Factors
IS - 4
ER -