Synergistic effects of C-peptide and insulin on low O2-induced ATP release from human erythrocytes
Synergistic effects of C-peptide and insulin on low O2-induced ATP release from human erythrocytes
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DOI：
10.1152/ajpregu.00341.2013
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发表时间：
2013-12-01
影响因子：
2.8
通讯作者：
Sprague, Randy S.
中科院分区：
文献类型：
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作者：
Richards, Jennifer P.;Stephenson, Alan H.;Sprague, Randy S.
红细胞通过释放O-2和血管扩张剂ATP参与骨骼肌中氧气（O-2）输送与局部需要的匹配。据报道，在具有胰岛素抵抗的人中发现的胰岛素浓度抑制低O-2诱导的ATP释放。然而，在体内，胰岛素与连接肽（C肽）以等摩尔浓度共释放，但由于胰岛素半衰期较短，肽以范围为1：1至6：1的C肽与胰岛素的比率循环。在这里，我们调查的假设，C-肽和胰岛素协同工作，以维持低O-2诱导的ATP从人红细胞释放。使用薄膜眼压计改变O-2张力，我们确定C肽或胰岛素单独以浓度依赖性方式抑制低O-2诱导的ATP释放;然而，以1：1的比例共同施用肽没有（n = 5; P < 0.05）。由于C肽与胰岛素的这种比例在体内不存在很长一段时间，我们还研究了额外的生理比例对ATP释放的影响。在存在空腹人体中发现的胰岛素浓度（0.05 nM）的情况下，C肽与胰岛素的比例为4：1和6：1不会对低O-2诱导的ATP释放产生不利影响。然而，在餐后条件下，在人外周循环中发现的胰岛素浓度（0.5 nM）下，C肽与胰岛素的比例为6：1抑制低O-2诱导的ATP释放（n = 5）。这些研究结果表明，迄今尚未认识到的C肽和胰岛素之间的协同作用，可能有生理上的重要性，在骨骼肌灌注分布的调节。
Erythrocytes participate in the matching of oxygen (O-2) delivery with local need in skeletal muscle via the release of O-2 and the vasodilator, ATP. It was reported that a concentration of insulin found in humans with insulin resistance inhibits low O-2-induced ATP release. However, in vivo, insulin is coreleased with connecting peptide (C-peptide) at equimolar concentrations, but because of the shorter insulin half-life, the peptides circulate at ratios of C-peptide to insulin ranging from 1:1 to 6:1. Here, we investigate the hypothesis that C-peptide and insulin work synergistically to maintain low O-2-induced ATP release from human erythrocytes. Using a thin-film tonometer to alter O-2 tension, we determined that either C-peptide or insulin alone inhibits low O-2-induced ATP release in a concentration-dependent manner; however, coadministration of the peptides at a 1:1 ratio does not (n = 5; P < 0.05). Because this ratio of C-peptide to insulin is not present in vivo for extended periods, we also investigated the effect of additional physiological ratios on ATP release. In the presence of insulin concentrations that would be found in fasting humans (0.05 nM), C-peptide to insulin ratios of 4:1 and 6:1 did not adversely affect low O-2-induced ATP release. However, at a concentration of insulin found in the peripheral circulation of humans under postprandial conditions (0.5 nM), a ratio of C-peptide to insulin of 6:1 inhibited low O-2-induced ATP release (n = 5). These findings demonstrate a heretofore unrecognized synergism between C-peptide and insulin that could have physiological importance in the regulation of perfusion distribution in skeletal muscle.