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Erythrocytes participate in the matching of oxygen (O²) delivery with local need in skeletal muscle via the release of O² and the vasodilator, ATP. It was reported that a concentration of insulin found in humans with insulin resistance inhibits low O²-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 O²-induced ATP release from human erythrocytes. Using a thin-film tonometer to alter O² tension, we determined that either C-peptide or insulin alone inhibits low O²-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 O²-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 O²-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. [ABSTRACT FROM AUTHOR]

Exercise-induced expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is dramatically inhibited in mice pretreated with a 3-adrenergic receptor (β-AR) antagonist, suggesting that β-ARs play an important role in the regulation of skeletal muscle PGC-1α expression, and potentially, mitochondrial biogenesis. Accordingly, we hypothesized that acute β-AR stimulation would induce transcriptional pathways involved in skeletal muscle mitochondrial biogenesis in humans. Whole body protein turnover (WBPT), myofibrillar protein synthesis (MyPS), skeletal muscle mitochondrial protein synthesis (MiPS), and mitochondrial biogenic signaling were determined in samples of vastus lateralis obtained on two separate occasions in 10 young adult males following 1 h of continuous intravenous administration of saline (CON) or a nonspecific β-AR agonist [isoproterenol (ISO): 12 ng·kg fat free mass-1·min-1], combined with coinfusion of [1,2]13C-leucine. β-AR stimulation induced appreciable increases in heart rate and systolic blood pressure (both P < 0.001) but did not affect mitochondrial biogenic signaling (no change in PGC-1α, TFAM, NRF-1, NRF-2, COX, or NADHox expression via RT-PCR; P> 0.05). Additionally, MiPS [CON: 0.099 ± 0.028, ISO: 0.074 ± 0.046 (mean ± SD); P > 0.05] and MyPS (CON: 0.059 ± 0.008, ISO: 0.055 ± 0.009; P > 0.05), as well as measures of WBPT were unaffected. On the basis of this investigation, we conclude that acute intravenous β-AR stimulation does not increase mitochondrial protein synthesis or biogenesis signals in skeletal muscle. [ABSTRACT FROM AUTHOR]