Prevention of vascular and neural dysfunction in diabetic rats by C-peptide

Prevention of vascular and neural dysfunction in diabetic rats by C-peptide
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DOI:
10.1126/science.277.5325.563
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发表时间:
1997-07-25
期刊:
影响因子:
56.9
通讯作者:
Williamson, JR
Williamson, JR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ido, Y;Vindigni, A;Williamson, JR

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C肽是胰岛素原加工为胰岛素过程中的一种裂解产物,除了参与胰岛素合成外,一直被认为几乎没有任何生物活性。给糖尿病大鼠注射人C肽可预防或减轻血管和神经(电生理)功能障碍以及组织中依赖钠和钾的三磷酸腺苷活性受损。该肽中部的非极性氨基酸是产生这些生物效应所必需的。合成的反向序列(逆序)和全D - 氨基酸(对映体)C肽与天然C肽具有同等效力,这表明C肽对糖尿病血管和神经功能障碍的影响是由非手性相互作用介导的,而非立体特异性受体或结合位点。
C-peptide, a cleavage product from the processing of proinsulin to insulin, has been considered to possess little if any biological activity other than its participation in insulin synthesis, Injection of human C-peptide prevented or attenuated vascular and neural (electrophysiological) dysfunction and impaired Na+- and K+-dependent adenosine triphosphate activity in tissues of diabetic rats. Nonpolar amino acids in the midportion of the peptide were required for these biological effects. Synthetic reverse sequence (retro) and all-D-amino acid (enantio) C-peptides were equipotent to native C-peptide, which indicates that the effects of C-peptide on diabetic vascular and neural dysfunction were mediated by nonchiral interactions instead of stereospecific receptors or binding sites.