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首页> 外文期刊>American Journal of Physiology >Mechanisms of C-peptide-mediated rescue of low 02-induced ATP releasefrom erythrocytes of humans with Type 2 diabetes
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Mechanisms of C-peptide-mediated rescue of low 02-induced ATP releasefrom erythrocytes of humans with Type 2 diabetes

机译：具有2型糖尿病的人类红细胞红细胞的C-肽介导的低02诱导的ATP释放机制

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The circulating erythro-cyte, by virtue of the regulated release of ATP in response to reducedoxygen (O2) tension, plays a key role in maintaining appropriateperfusion distribution to meet tissue needs. Erythrocytes from indi-viduals with Type 2 diabetes (DM2) fail to release ATP in response tothis stimulus. However, the administration of C-peptide and insulin ata 1:1 ratio was shown to restore this important physiological responsein humans with DM2. To begin to investigate the mechanisms bywhich C-peptide influences low 02-induced ATP release, erythrocytesfrom healthy humans and humans with DM2 were exposed to reduced02 in a thin-film tonometer, and ATP release under these conditionswas compared with release during normoxia. We determined that 1)low 02-induced ATP release from DM2 erythrocytes is rescued byC-peptide in the presence and absence of insulin, 2) the signalingpathway activated by C-peptide in human erythrocytes involves PKC,as well as soluble guanylyl cyclase (sGC) and J) inhibitors of cGMPdegradation rescue low 02-induced ATP release from DM2 erythro-cytes. These results provide support for the hypothesis that both PKCand sGC are components of a signaling pathway activated by C-pep-tide in human erythrocytes. In addition, since both C-peptide andphosphodiesterase 5 inhibitors rescue low 02-induced ATP releasefrom erythrocytes of humans with DM2, their administration tohumans with DM2 could aid in the treatment and/or prevention of thevascular disease associated with this condition.microcirculation; adenosine triphosphate; G protein-coupled receptor146; red blood cell; soluble guanylyl cyclasethe appropriate delivery of oxygen and nutrients to skeletalmuscle is required for normal physiological function. It hasbeen suggested that the circulating erythrocyte, by virtue of theregulated release of ATP in response to physiological stimuli,plays a key role in maintaining optimal perfusion distributionto meet tissue needs. When erythrocytes pass through areas ofskeletal muscle with a decreased Po2, oxygen is released,which initiates a signal transduction pathway, resulting in therelease of ATP. This important physiological response contrib-utes to the distribution of perfusion to supply adequate bloodflow (O2 supply) to specific regions of skeletal muscle.
机译：循环红细胞，借助于响应于SpooreOxygen（O2）张力的ATP释放，在维持适当的灌注分布以满足组织需求方面发挥关键作用。来自2型糖尿病（DM2）的INDI-viduals的红细胞未能在响应刺激刺激中释放ATP。然而，显示C-肽和胰岛素ATA 1：1的施用比例恢复与DM2的这种重要的生理反应。为了开始探讨该机制，通过多02诱导的ATP释放的C-肽影响，在薄膜眼压计的薄膜眼压计中暴露于薄膜眼压计中的ERYTHROCYTESFROM健康的人和人类在薄膜眼压计下，与常氧释放相比，在这些条件下的ATP释放。我们确定1）从DM2诱导的ATP释放来自DM2红细胞在存在和不存在胰岛素的情况下拯救副肽，2）由人红细胞中的C-肽激活的信号通路涉及PKC，以及可溶性观冠酶（SGC ）和j）CgMp xegradation的抑制剂拯救低02诱导的ATP释放从DM2红细胞细胞中释放。这些结果提供了对假设的支持，即PKCAND SGC是由人红细胞中的C-Pep-ide激活的信号通路的组分。此外，由于C-肽亚磷酸酯酶5抑制剂抑制低02诱导的ATP释放，从DM2的人体中促使人类红细胞，其施用与DM2的施用可以有助于治疗和/或预防与这种条件相关的血管疾病。腺苷三磷酸; G蛋白偶联受体146;红细胞;可溶性观光环酰基适当地递送氧气和营养素到骨骼瓣的正常生理功能。它已经显示出循环红细胞，凭借在响应生理刺激的ATP释放的循环红细胞，在保持最佳灌注分布符合组织需求方面发挥着关键作用。当红细胞通过具有降低的PO2的骨骼肌区域时，释放氧气，该氧气引发信号转导途径，导致ATP的释放。这种重要的生理反应贡献 - 灌注分配给灌注，为骨骼肌的特定区域提供足够的血流（O2供应）。

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