Low O2-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin
Low O2-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin
复制标题
DOI：
10.1152/ajpregu.00206.2014
复制
发表时间：
2014-10-01
影响因子：
2.8
通讯作者：
Sprague, Randy S.
中科院分区：
文献类型：
--
作者：
Richards, Jennifer P.;Yosten, Gina L. C.;Sprague, Randy S.
红细胞释放ATP以响应降低的氧（O-2）张力刺激局部血管舒张，使这些细胞能够直接灌注到骨骼肌中需要O-2的区域。2型糖尿病患者的红细胞不会响应低O-2而释放ATP。C-肽和胰岛素单独抑制低O-2诱导的ATP从健康人红细胞的释放，但当在生理浓度和比例共同给药时，没有看到抑制。在这里，我们确定：1）健康人和患有2型糖尿病的人的红细胞具有C-肽受体（GPR 146），2）生理比例的C-肽和胰岛素的组合挽救了来自患有2型糖尿病的人的红细胞的低O-2诱导的ATP释放，3）在患有2型糖尿病的人中报道的残余C肽水平不足以在1 nM胰岛素存在下挽救低O-2诱导的ATP释放，和4）C肽和胰岛素的作用既不因葡萄糖水平的增加而改变，也不因红细胞变形能力的改变而解释。这些结果表明，在2型糖尿病的治疗方案中加入C肽可能对组织氧合具有有益作用，这将有助于改善伴随的外周血管疾病。
ATP release from erythrocytes in response to reduced oxygen (O-2) tension stimulates local vasodilation, enabling these cells to direct perfusion to areas in skeletal muscle in need of O-2. Erythrocytes of humans with type 2 diabetes do not release ATP in response to low O-2. Both C-peptide and insulin individually inhibit low O-2-induced ATP release from healthy human erythrocytes, yet when coadministered at physiological concentrations and ratios, no inhibition is seen. Here, we determined: that 1) erythrocytes of healthy humans and humans with type 2 diabetes possess a C-peptide receptor (GPR146), 2) the combination of C-peptide and insulin at physiological ratios rescues low O-2-induced ATP release from erythrocytes of humans with type 2 diabetes, 3) residual C-peptide levels reported in humans with type 2 diabetes are not adequate to rescue low O-2-induced ATP release in the presence of 1 nM insulin, and 4) the effects of C-peptide and insulin are neither altered by increased glucose levels nor explained by changes in erythrocyte deformability. These results suggest that the addition of C-peptide to the treatment regimen for type 2 diabetes could have beneficial effects on tissue oxygenation, which would help to ameliorate the concomitant peripheral vascular disease.