Reversal of streptozotocin-induced hyperglycemia by continuous supply of betacellulin in mice
Reversal of streptozotocin-induced hyperglycemia by continuous supply of betacellulin in mice
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DOI：
10.1080/08977190802136854
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发表时间：
2008-01
期刊：
影响因子：
1.8
通讯作者：
Yoritsuna Yamamoto;S. Yamada;T. Kodera;Akemi Hara;K. Motoyoshi;Yuji Tanaka;Tadahiro Nagaoka;M. Seno;I. Kojima
中科院分区：
文献类型：
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作者：
Yoritsuna Yamamoto;S. Yamada;T. Kodera;Akemi Hara;K. Motoyoshi;Yuji Tanaka;Tadahiro Nagaoka;M. Seno;I. Kojima
先前的研究表明β细胞素（BTC）具有促进β细胞再生的功效。然而，由于其半衰期较短，比特币的影响可能被低估了。本研究旨在评估持续施用 BTC 对 β 细胞再生的影响。制备编码proBTC（Ad-proBTC）和成熟BTC（Ad-mBTC）的腺病毒载体，并比较在AML12肝细胞中分泌BTC的功效。当AML12细胞感染Ad-proBTC或Ad-mBTC时，感染Ad-mBTC的细胞分泌出相当多的BTC。然后我们将 Ad-mBTC 注入小鼠尾静脉。肝脏中检测到 BTC 表达至少 21 天，血清 BTC 维持在约 1 ng/ml 7 天。当给予STZ（170mg/kg）后立即输注Ad-mBTC时，STZ引起的血浆葡萄糖升高被显着抑制，并且血浆葡萄糖浓度在21天内保持在低于200mg/dl。 Ad-mBTC 输注小鼠的胰岛素含量和 β 细胞质量显着增加。这些结果表明，持续施用BTC对于促进β细胞再生非常有效。
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.