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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A transgene coding for a human insulin analog has a mitogenic effect on murine embryonic beta cells.
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A transgene coding for a human insulin analog has a mitogenic effect on murine embryonic beta cells.

机译：编码人胰岛素类似物的转基因对鼠胚胎β细胞具有促有丝分裂作用。

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摘要

We have investigated the mitogenic effect of three mutant forms of human insulin on insulin-producing beta cells of the developing pancreas. We examined transgenic embryonic and adult mice expressing (i) human [AspB10]-proinsulin/insulin ([AspB10]ProIN/IN), produced by replacement of histidine by aspartic acid at position 10 of the B chain and characterized by an increased affinity for the insulin receptor; (ii) human [LeuA3]insulin, produced by the substitution of leucine for valine in position 3 of the A chain, which exhibits decreased receptor binding affinity; and (iii) human [LeuA3, AspB10]insulin "double" mutation. During development, beta cells of AspB10 embryos were twice as abundant and had a 3 times higher rate of proliferation compared with beta cells of littermate controls. The mitogenic effect of [AspB10]ProIN/IN was specific for embryonic beta cells because the rate of proliferation of beta cells of adults and of glucagon (alpha) cells and adrenal chromaffin cells of embryos was similar in AspB10 mice and controls. In contrast to AspB10 embryos, the number of beta cells in the LeuA3 and "double" mutant lines was similar to the number in controls. These findings indicate that the [AspB10]ProIN/IN analog increased the rate of fetal beta-cell proliferation. The mechanism or mechanisms that mediate this mitogenic effect remain to be determined.
机译：我们已经研究了人类胰岛素的三种突变形式对发育中的胰腺产生胰岛素的β细胞的促有丝分裂作用。我们检查了表达（i）人[AspB10]-胰岛素原/胰岛素（[AspB10] ProIN / IN）的转基因胚胎小鼠和成年小鼠，它们是通过B链第10位的天冬氨酸置换组氨酸而产生的，其特征在于对胰岛素受体； （ii）通过用亮氨酸取代A链第3位的缬氨酸而产生的人[LeuA3]胰岛素，其受体结合亲和力降低； （iii）人[LeuA3，AspB10]胰岛素“双重”突变。在发育过程中，AspB10胚胎的β细胞比同窝对照的β细胞高出两倍，并且具有3倍的增殖速率。 [AspB10] ProIN / IN的促有丝分裂作用对胚胎β细胞具有特异性，因为成人的β细胞和胰高血糖素（alpha）细胞和肾上腺嗜铬细胞的增殖速率在AspB10小鼠和对照组中相似。与AspB10胚胎相反，LeuA3和“ double”突变株系中β细胞的数量与对照中的数量相似。这些发现表明[AspB10] ProIN / IN类似物增加了胎儿β细胞增殖的速率。介导这种促有丝分裂作用的一种或多种机制尚待确定。

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