期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 305, 期 11, 页码 R1331-R1336出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00341.2013
关键词
phosphodiesterase 3; UT-15C; diabetes; microcirculation; adenosine triphosphate
类别
资金
- American Diabetes Association [BS-150]
- National Institutes of Health [HL-089094]
Erythrocytes participate in the matching of oxygen (O-2) delivery with local need in skeletal muscle via the release of O-2 and the vasodilator, ATP. It was reported that a concentration of insulin found in humans with insulin resistance inhibits low O-2-induced ATP release. However, in vivo, insulin is coreleased with connecting peptide (C-peptide) at equimolar concentrations, but because of the shorter insulin half-life, the peptides circulate at ratios of C-peptide to insulin ranging from 1:1 to 6:1. Here, we investigate the hypothesis that C-peptide and insulin work synergistically to maintain low O-2-induced ATP release from human erythrocytes. Using a thin-film tonometer to alter O-2 tension, we determined that either C-peptide or insulin alone inhibits low O-2-induced ATP release in a concentration-dependent manner; however, coadministration of the peptides at a 1:1 ratio does not (n = 5; P < 0.05). Because this ratio of C-peptide to insulin is not present in vivo for extended periods, we also investigated the effect of additional physiological ratios on ATP release. In the presence of insulin concentrations that would be found in fasting humans (0.05 nM), C-peptide to insulin ratios of 4:1 and 6:1 did not adversely affect low O-2-induced ATP release. However, at a concentration of insulin found in the peripheral circulation of humans under postprandial conditions (0.5 nM), a ratio of C-peptide to insulin of 6:1 inhibited low O-2-induced ATP release (n = 5). These findings demonstrate a heretofore unrecognized synergism between C-peptide and insulin that could have physiological importance in the regulation of perfusion distribution in skeletal muscle.
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