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Regeneration of Pancreatic β-cells

胰腺 β 细胞的再生

基本信息

批准号：
09557073
负责人：
KOJIMA Itaru
金额：
$ 7.87万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

We studied differentiation factors involved in the formation of pancreatic beta cells using AR42J cells as a model system. We showed that activin A and betacellulin are able to induce differentiation into insulin-producing cells. To determine whether or not these two factors are involved in the differentiation of pancreatic beta cells, we then studied the expression of these factors in the regenerating pancreas. Activin A was expressed in ductal cells of the pancreas and in newly-formed endocrine cells. Betacellulin was expressed in newly-formed endocrine cells. These results are consistent with the notion that these two factors are involved in the islet neogenesis. We therefore examined whether or not these factors are effective in promoting islet neogenesis. We found that exogenous activin A was not effective. However, betacellulin was quite effective in promoting islet neogenesis. Thus, Betacellulin enhanced the formation of endocrine cells in 90% pancreatectomized rats and increased the number of islets in remnant pancreas. Furthermore, plasma glucose after the administration of ip glucose was lower in betacellulin-treated rats and the plasma insulin concentrations were higher in betacellulin-treated rats. Betacellulin also increased the insulin content of the remnant pancreas. These results indicate that betacellulin is effective in promoting regeneration of pancreatic islets after 90% pancreatectomy. Betacellulin is a potential factor to promote islet regeneration.

我们以AR42J细胞为模型系统，研究了参与胰岛β细胞形成的分化因素。我们发现激活素A和β细胞蛋白能够诱导分化为产生胰岛素的细胞。为了确定这两个因子是否参与了胰腺β细胞的分化，我们随后研究了这些因子在再生胰腺中的表达。激活素A在胰腺导管细胞和新形成的内分泌细胞中表达。β细胞蛋白在新形成的内分泌细胞中表达。这些结果与这两个因素参与胰岛新生的观点是一致的。因此，我们检查了这些因素在促进胰岛新生方面是否有效。我们发现外源激活素A不起作用。而β-纤维素对胰岛新生有较好的促进作用。因此，Betacellin促进了90%的胰腺切除大鼠内分泌细胞的形成，并增加了残余胰腺中的胰岛数量。此外，β-纤维素处理组大鼠在ip葡萄糖后血糖较低，而血浆胰岛素浓度较高。Betacellin还能增加残存胰腺中的胰岛素含量。这些结果表明，β细胞蛋白对90%的胰腺切除后的胰岛再生有促进作用。β-纤维素是促进胰岛再生的潜在因素。