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.

中文翻译：

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通过持续供应小鼠β-纤维素来逆转链脲佐菌素诱导的高血糖。

以前的研究表明，β-纤维素（BTC）可以促进β-细胞再生。但是，由于其半衰期短，BTC的效果可能被低估了。进行该研究以评估连续施用BTC对β细胞再生的影响。制备了编码proBTC（Ad-proBTC）和成熟BTC（Ad-mBTC）的腺病毒载体，并比较了AML12肝细胞中BTC分泌的功效。当用Ad-proBTC或Ad-mBTC感染AML12细胞时，用Ad-mBTC感染的细胞会分泌大量的BTC。然后，我们将Ad-mBTC注入小鼠尾静脉。在肝脏中检测到BTC的表达至少21天，并且将血清BTC维持在约1 ng / ml的水平7天。服用STZ（170 mg / kg）后立即注入Ad-mBTC，STZ诱导的血浆葡萄糖升高明显受到抑制，并且血浆葡萄糖浓度在小于200mg / dl的条件下保持21天。在注入Ad-mBTC的小鼠中，胰岛素含量和β细胞质量显着增加。这些结果表明，连续施用BTC在促进β细胞再生方面非常有效。