Reversal of streptozotocin-induced hyperglycemia by continuous supply of betacellulin in mice

Yoritsuna Yamamoto, Satoko Yamada, Tsutomu Kodera, Akemi Hara, Kazuo Motoyoshi, Yuji Tanaka, Tadahiro Nagaoka, Masaharu Seno, Itaru Kojima

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalGrowth Factors
Issue number4
Publication statusPublished - 2008


  • Betacellulin
  • Diabetes
  • Differentiation
  • Insulin
  • Regeneration
  • β-cell

ASJC Scopus subject areas

  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology


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