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Mechanisms of C-peptide-mediated rescue of low O2-induced ATP release from erythrocytes of humans with Type 2 diabetes.
- Source :
-
American Journal of Physiology: Regulatory, Integrative & Comparative Physiology . 3/1/2015, Vol. 308 Issue 5, pR411-R418. 8p. - Publication Year :
- 2015
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03636119
- Volume :
- 308
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Regulatory, Integrative & Comparative Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 101382105
- Full Text :
- https://doi.org/10.1152/ajpregu.00420.2014