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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Biosynthetic 20-kilodalton methionyl-human growth hormone has diabetogenic and insulin-like activities.
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Biosynthetic 20-kilodalton methionyl-human growth hormone has diabetogenic and insulin-like activities.

机译：生物合成的20公斤甲硫氨酸-人生长激素具有促糖尿病和类胰岛素的活性。

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The anterior pituitary gland produces a 20-kilodalton (kDa) variant of human growth hormone (hGH) that differs from the predominant 22-kDa form of hGH in that amino acid residues 32-46 are deleted. Previous work has suggested that the 20-kDa variant possesses the full growth-promoting and lactogenic activities of 22-kDa hGH but lacks its intrinsic diabetogenic and insulin-like activities. In the present study, recombinant DNA techniques were used to prepare biosynthetic 20-kDa hGH, and some of the biological properties of the purified hGH variant were examined. The biosynthetic 20-kDa hGH variant was found to share the propensity for aggregation exhibited by its native counterpart. Moreover, like the native variant, biosynthetic 20-kDa hGH possessed full growth-promoting activity in the weight gain test in hypophysectomized rats. However, contrary to previous work suggesting that native 20-kDa hGH lacks diabetogenic and insulin-like activities, biosynthetic 20-kDa hGH was found to have substantial diabetogenic activity when administered chronically to ob/ob mice and to possess approximately 20% the in vitro insulin-like activity of biosynthetic 22-kDa hGH on isolated epididymal adipose tissue of hypophysectomized rats. The diabetogenic and insulin-like activities of biosynthetic 20-kDa hGH cannot be ascribed to contamination of the hormone preparation with the 22-kDa form of hGH or with other diabetogenic or insulin-like pituitary peptides. Therefore, the results strongly suggest that diabetogenic and insulin-like activities are also intrinsic properties of the 20-kDa variant of hGH.
机译：垂体前叶产生人类生长激素（hGH）的20千达尔顿（kDa）变异体，与hGH的主要22-kDa形式不同之处在于氨基酸残基32-46被删除。先前的工作表明20 kDa变体具有22 kDa hGH的全部促生长和生乳活性，但缺乏其固有的糖尿病和胰岛素样活性。在本研究中，重组DNA技术用于制备生物合成的20 kDa hGH，并检查了纯化的hGH变体的一些生物学特性。发现生物合成的20-kDa hGH变体具有与其天然对应物表现出的聚集倾向。此外，像天然变体一样，在垂体切除的大鼠的体重增加测试中，生物合成的20 kDa hGH具有完全的促生长活性。然而，与先前的研究表明天然的20-kDa hGH缺乏糖尿病和胰岛素样活性相反，发现将生物合成的20-kDa hGH长期施用于ob / ob小鼠具有显着的糖尿病形成活性，并在体外具有约20％的活性。生物合成的22 kDa hGH对垂体切除的大鼠附睾脂肪组织的胰岛素样活性。生物合成的20 kDa hGH的致糖尿病和胰岛素样活性不能归因于激素制剂受到22 kDa形式的hGH或其他致糖尿病或胰岛素样垂体肽的污染。因此，结果有力地表明，致糖尿病和胰岛素样活性也是hGH的20 kDa变异体的固有特性。

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