Signalling mechanisms involved in C-peptide-mediated inhibition of low O2-induced ATP release from human erythrocytes

摘要: Background and objectives In vivo, insulin is released with connecting peptide (C-peptide) which has recently been shown to have biological activity. When erythrocytes are exposed reduced oxygen (O2) tension, they release O2 as well the vasodilator ATP enabling them participate in appropriate distribution of vascular perfusion and, thereby, supply. Low O2-induced absent humans type 2 diabetes (DM2), but this response restored by co-administration physiological concentrations C-peptide. However, either C-peptide or insulin, when administered alone, inhibits low from healthy human erythrocytes. Here, we investigated mechanism(s) erythrocytes. Methods Erythrocytes (n = 21) DM2 (n = 4) were incubated absence presence inhibitors protein kinase C alpha (PKCα) soluble guanylyl cyclase (sGC). Erythrocytes then O2, was determined. Results In erythrocytes, inhibited O2. Preincubation Go6976, a PKCα inhibitor, ODQ, sGC prevented effect In addition, alone did not rescue erythrocytes. Conclusion Administration excess levels present under conditions combination at ratios that exceed those observed physiologically insulin-deficient individuals can be detrimental for could, consequently, interfere optimal delivery skeletal muscle.