Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Biochem Biophys Res Commun. 2010 Jan 15;391(3):1561-6. doi: 10.1016/j.bbrc.2009.12.125. Epub 2009 Dec 28.
Three principally different sites of action have been reported for proinsulin C-peptide, at surface-mediated, intracellular, and extracellular locations. Following up on the latter, we now find that (i) mass spectrometric analyses reveal the presence of the C-peptide monomer in apparent equilibrium with a low-yield set of oligomers in weakly acidic or basic aqueous solutions, even at low peptide concentrations (sub-muM). It further shows not only C-peptide to interact with insulin oligomers (known before), but also the other way around. (ii) Polyacrylamide gel electrophoresis of C-peptide shows detectable oligomers upon Western blotting. Formation of thioflavin T positive material was also detected. (iii) Cleavage patterns of analogues are compatible with C-peptide as a substrate of insulin degrading enzyme. Combined, the results demonstrate three links with insulin properties, in a manner reminiscent of amyloidogenic peptides and their chaperons in other systems. If so, peripheral C-peptide/insulin interactions, absolute amounts of both peptides and their ratios may be relevant to consider in diabetic and associated diseases.
目前已报道胰岛素原 C 肽有三种主要的作用部位，分别位于表面介导部位、细胞内和细胞外位置。在对后者进行研究后，我们现在发现：（i）质谱分析显示 C 肽单体与低产量的寡聚物处于平衡状态，即使在低肽浓度（亚微摩尔）下也是如此。这进一步表明 C 肽不仅与胰岛素寡聚物相互作用（这是以前就知道的），而且反之亦然。（ii）聚丙烯酰胺凝胶电泳显示 C 肽经 Western 印迹后可检测到寡聚物。还检测到硫代黄素 T 阳性物质的形成。（iii）类似物的切割模式与 C 肽作为胰岛素降解酶的底物相兼容。综合来看，这些结果表明 C 肽与胰岛素的特性有三个联系，这与其他系统中的淀粉样肽及其伴侣相似。如果是这样，外周 C 肽/胰岛素的相互作用、两种肽的绝对含量及其比例可能与糖尿病和相关疾病有关。
