Skeletal muscle interleukin-6 and tumor necrosis factor-α release in healthy subjects and patients with type 2 diabetes at rest and during exercise

Febbraio, Mark A.; Steensberg, Adam; Starkie, Rebecca L.; McConell, Glenn K.; Kingwell, Bronwyn A.

doi:10.1016/s0026-0495(03)00105-7

Cited by 71 publications

(73 citation statements)

References 26 publications

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“…The most likely explanation for this paradox is that vaspin serum concentration is differentially regulated in the resting state and after exercise. Similar to our observations for vaspin serum concentrations, interleukin-6 is increased during and after exercise, whereas in the resting state elevated circulating interleukin-6 correlates with increased BMI and decreased insulin sensitivity (21). Moreover, elevated vaspin concentrations after 4 weeks of intensive physical training might represent a transient adaptation mechanism because competitive sportsmen with long-term physical training had significantly lower vaspin serum concentration than untrained age-and BMI-matched control subjects.…”

Section: Discussionsupporting

confidence: 84%

“…While the human embryonic kidney (HEK) 293 cell-expressed vaspin was used for recombinant human vaspin, standard E. coli-expressed vaspin was used as an immunogen for generating human vaspin-specific monoclonal and polyclonal Abs. For making recombinant vaspin proteins in HEK293 cells and E. coli, the portion of the geneencompassing presumed mature polypeptides, Leu 21 through Lys 414 , was amplified and digested with appropriate restriction enzymes and then cloned into both pAGNF (AdipoGen, Seoul, Korea) and pET21a (Novagen, Madison, WI). pAGNF is an in-house eukaryotic vector whose expression is driven by the cytomegalovirus early promoter and secretion is facilitated by the plasminogen activator inhibitor type I (PAI-1) leader peptide.…”

Section: Methodsmentioning

confidence: 99%

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Serum Vaspin Concentrations in Human Obesity and Type 2 Diabetes

Youn

Klöting²,

Kratzsch³

et al. 2008

Diabetes

382

347

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OBJECTIVE-Vaspin was identified as an adipokine with insulin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in a rat model of type 2 diabetes. We have recently shown that vaspin mRNA expression in adipose tissue is related to parameters of obesity and glucose metabolism. However, the regulation of vaspin serum concentrations in human obesity and type 2 diabetes is unknown.RESEARCH DESIGN AND METHODS-For the measurement of vaspin serum concentrations, we developed an enzyme-linked immunosorbent assay (ELISA). Using this ELISA, we assessed circulating vaspin in a cross-sectional study of 187 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes before and after a 4-week physical training program.RESULTS-Vaspin serum concentrations were significantly higher in female compared with male subjects. There was no difference in circulating vaspin between individuals with NGT and type 2 diabetes. In the normal glucose-tolerant group, circulating vaspin significantly correlated with BMI and insulin sensitivity. Moreover, physical training for 4 weeks resulted in significantly increased circulating vaspin levels.CONCLUSIONS-We found a sexual dimorphism in circulating vaspin. Elevated vaspin serum concentrations are associated with obesity and impaired insulin sensitivity, whereas type 2 diabetes seems to abrogate the correlation between increased circulating vaspin, higher body weight, and decreased insulin sensitivity. Low circulating vaspin correlates with a high fitness level, whereas physical training in untrained individuals causes increased vaspin serum concentrations.

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Section: Discussionsupporting

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Serum Vaspin Concentrations in Human Obesity and Type 2 Diabetes

Youn

Klöting²,

Kratzsch³

et al. 2008

Diabetes

382

347

View full text Add to dashboard Cite

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“…It is possible that the capacity for hepatosplanchnic IL-6 uptake cannot match the rate of contracting limb IL-6 release, because of the large differences in blood flow to these regions during exercise. We have previously measured leg blood flow during similar exercise to be at least threefold higher (7,8) than the hepatosplanchnic blood flow reported in the present study (Fig. 1).…”

Section: Discussionsupporting

confidence: 57%

“…Rather, muscle contraction rapidly increases intramuscular IL-6 gene expression (7,15,23,33,35,37) and the nuclear transcriptional activity of IL-6 (15). Importantly, IL-6 protein is released from skeletal muscle during prolonged exercise (7,8,32,33,35), and cultured human primary muscle cells are capable of increasing IL-6 mRNA when incubated with the calcium ionophore ionomycin (14). Therefore, it is likely that myocytes produce IL-6 in response to physical stress, and production of IL-6 by such tissue can account for most of the exercise-induced increase in plasma levels of this cytokine.…”

mentioning

confidence: 99%

Hepatosplanchnic clearance of interleukin-6 in humans during exercise

Febbraio

Ott

Nielsen

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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The cytokine interleukin (IL)-6 can increase markedly in the circulation during exercise, but whether the liver is a source of this increase is unknown. The aim of this study was to measure IL-6 flux across the hepatosplanchnic tissues in humans. To elevate systemic concentrations of IL-6, six healthy male subjects performed 120 min of semirecumbent cycling, and blood samples were simultaneously obtained from a brachial artery and the hepatic vein before and during exercise for the analysis of IL-6. Hepatosplanchnic blood flow (HBF) was measured using the indocyanine green infusion technique. Net hepatosplanchnic IL-6 balance was calculated from these measures. HBF was 1.3 ± 0.1 l/min at rest and was not reduced throughout exercise, averaging 1.1 ± 0.2 l/min. Arterial plasma IL-6 markedly increased ( P < 0.05) from 1.8 ± 0.6 ng/l at rest to 14.3 ± 3.2 ng/l after 120 min of exercise. The hepatosplanchnic viscera did not contribute to this increase, since there was a net hepatosplanchnic IL-6 uptake (0.8 ± 0.3 vs. 5.5 ± 1.9 ng/min, rest vs. 120 min; P < 0.05). These data demonstrate that the hepatosplanchnic viscera remove IL-6 from the circulation in humans. This removal may constitute a mechanism limiting the negative chronic metabolic action of chronically elevated circulating IL-6.

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“…Kawaguchi et al (2011) conducted an experiment in which twelve patients with nonalcoholic fatty liver disease (NAFLD) who were resistant to lifestyle counseling exercised with HTS in the lower extremities twice a week for 12 weeks. They reported that HTS exercise improved hepatic steatosis, insulin resistance and serum IL-6 levels in NAFLD patients (Kawaguchi et al 2011). Febbraio et al (2003 reported that plasma IL-6 doubled after 25 minutes of supine bicycle exercise at 60% V 4 O 2peak and this significant result suggested that IL-6 production was related to the mass of muscle activated.…”

Section: Interleukin-6mentioning

confidence: 99%

Cycling Exercise with Electrical Stimulation of Antagonist Muscles Increases Plasma Growth Hormone and IL-6

Omoto

Matsuse

Hashida

et al. 2015

Tohoku J. Exp. Med.

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Performing aerobics and resistance exercise at exactly the same time has not been available although combining both types of exercise in one training program has been attempted. The hybrid training system (HTS) is a resistance exercise that combines voluntary concentric muscle contractions with electrically stimulated eccentric muscle contractions. We devised an exercise technique using HTS on a cycle ergometer (HCE). Growth hormone (GH) and lactate are indicators of adequate training intensity. Interleukin-6 (IL-6) reflects enhancing lipid metabolism. The purpose of this study was to show that HCE provides sufficient exercise to stimulate the secretion of GH, lactate and IL-6. We compared an HCE test with cycle ergometer alone (CE). Ten healthy male subjects performed HCE and CE tests for 30 minutes each. The workload of both tests was set the same at 40% of each subject's peak oxygen uptake. For HCE, 2-minute HTS and 1-minute rest intervals were repeated. GH, lactate, and IL-6 were evaluated before and immediately after exercise, and at 15, 30 and 60 minutes. GH and lactate increased immediately after HCE. Moreover, the degree of the increases in GH after HCE (0 and 15 minutes) was higher than that after CE. IL-6 increased after HCE at 30 min, and the rate of change was higher than for CE. These results showed that HCE was more efficient in stimulating acute increases in GH, lactate and IL-6 than CE at the same workload. We may be able to combine electrically stimulated resistance exercise with aerobic exercise using HCE.

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Skeletal muscle interleukin-6 and tumor necrosis factor-α release in healthy subjects and patients with type 2 diabetes at rest and during exercise

Cited by 71 publications

References 26 publications

Serum Vaspin Concentrations in Human Obesity and Type 2 Diabetes

Serum Vaspin Concentrations in Human Obesity and Type 2 Diabetes

Hepatosplanchnic clearance of interleukin-6 in humans during exercise

Cycling Exercise with Electrical Stimulation of Antagonist Muscles Increases Plasma Growth Hormone and IL-6

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