Reversal of streptozotocin-induced hyperglycemia by continuous supply of betacellulin in mice.
Previous studies have shown the efficacy of betacellulin (BTC) to promote beta-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 beta-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 beta-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 beta-cells.
Yamamoto
Yoritsuna
Y
Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Yamada
Satoko
S
Kodera
Tsutomu
T
Hara
Akemi
A
Motoyoshi
Kazuo
K
Tanaka
Yuji
Y
Nagaoka
Tadahiro
T
Seno
Masaharu
M
Kojima
Itaru
I
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D066259:Betacellulin; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D005822:Genetic Vectors; D022781:Hepatocytes / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin / Q000494:pharmacology*
D066259:Betacellulin; D001786:Blood Glucose; C587852:Btc protein, mouse; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D013311:Streptozocin