Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 308 (5), R411-8

Mechanisms of C-peptide-mediated Rescue of Low O2-induced ATP Release From Erythrocytes of Humans With Type 2 Diabetes

Affiliations

Mechanisms of C-peptide-mediated Rescue of Low O2-induced ATP Release From Erythrocytes of Humans With Type 2 Diabetes

Jennifer P Richards et al. Am J Physiol Regul Integr Comp Physiol.

Abstract

The circulating erythrocyte, by virtue of the regulated release of ATP in response to reduced oxygen (O2) tension, plays a key role in maintaining appropriate perfusion distribution to meet tissue needs. Erythrocytes from individuals with Type 2 diabetes (DM2) fail to release ATP in response to this stimulus. However, the administration of C-peptide and insulin at a 1:1 ratio was shown to restore this important physiological response in humans with DM2. To begin to investigate the mechanisms by which C-peptide influences low O2-induced ATP release, erythrocytes from healthy humans and humans with DM2 were exposed to reduced O2 in a thin-film tonometer, and ATP release under these conditions was compared with release during normoxia. We determined that 1) low O2-induced ATP release from DM2 erythrocytes is rescued by C-peptide in the presence and absence of insulin, 2) the signaling pathway activated by C-peptide in human erythrocytes involves PKC, as well as soluble guanylyl cyclase (sGC) and 3) inhibitors of cGMP degradation rescue low O2-induced ATP release from DM2 erythrocytes. These results provide support for the hypothesis that both PKC and sGC are components of a signaling pathway activated by C-peptide in human erythrocytes. In addition, since both C-peptide and phosphodiesterase 5 inhibitors rescue low O2-induced ATP release from erythrocytes of humans with DM2, their administration to humans with DM2 could aid in the treatment and/or prevention of the vascular disease associated with this condition.

Keywords: G protein-coupled receptor 146; adenosine triphosphate; microcirculation; red blood cell; soluble guanylyl cyclase.

Similar articles

See all similar articles

Cited by 3 articles

Publication types

MeSH terms

LinkOut - more resources

Feedback