Untitled

Pedersen, Bente Klarlund; Steensberg, Adam; Fischer, Christian P.; Keller, Charlotte; Keller, Pernille; Plomgaard, Peter; Febbraio, Mark A.; Saltin, Bengt

doi:10.1023/a:1026070911202

Cited by 421 publications

(155 citation statements)

References 86 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…However, there is also the possibility that impaired muscle glycogen metabolism affects liver deposits indirectly via interleukin-6 (IL-6). It has been reported that exercise causes muscle to increase secretion of IL-6, which in turn signals to the liver to increase glycogen breakdown (27,28). Furthermore, IL-6 production by the muscle is increased as glycogen is depleted (29,30).…”

Section: Discussionmentioning

confidence: 99%

Exercise Capacity of Mice Genetically Lacking Muscle Glycogen Synthase

Pederson

Cope

Schroeder

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

The glucose storage polymer glycogen is generally considered to be an important source of energy for skeletal muscle contraction and a factor in exercise endurance. A genetically modified mouse model lacking muscle glycogen was used to examine whether the absence of the polysaccharide affects the ability of mice to run on a treadmill. The MGSKO mouse has the GYS1 gene, encoding the muscle isoform of glycogen synthase, disrupted so that skeletal muscle totally lacks glycogen. The morphology of the soleus and quadriceps muscles from MGSKO mice appeared normal. MGSKO-null mice, along with wild type littermates, were exercised to exhaustion. There were no significant differences in the work performed by MGSKO mice as compared with their wild type littermates. The amount of liver glycogen consumed during exercise was similar for MGSKO and wild type animals. Fasting reduced exercise endurance, and after overnight fasting, there was a trend to reduced exercise endurance for the MGSKO mice. These studies provide genetic evidence that in mice muscle glycogen is not essential for strenuous exercise and has relatively little effect on endurance.The two major repositories of glycogen, the polymeric storage form of glucose, are in the liver and skeletal muscle (1). In humans, these carbohydrate reserves are an important determinant of endurance upon sustained exercise, and muscle glycogen has long been viewed as a critical energy source during muscular activity (2-4). Depletion of muscle glycogen results in fatigue and impaired muscle performance and is a major determinant of endurance (2-5). Likewise, the ineffective utilization of muscle glycogen, as in patients with McArdle disease, leads to impaired exercise tolerance (6). In their "glycogen shunt" hypothesis, Shulman and Rothman (7) propose that glycogenolysis is the predominant source of energy for muscle contraction with glycogen acting essentially as an intermediate for blood glucose to enter glycolysis. Increasing muscle glycogen by manipulating diet and exercise regimens, a procedure termed "carbohydrate loading" or "glycogen supercompensation" (8), is adopted by endurance athletes to delay the onset of fatigue (4, 9 -11).Although the importance of adequate muscle glycogen to sustain exercise in humans has been well documented, caution is needed in extrapolating findings in rodents to humans. For instance, the amount of muscle glycogen, expressed as a fraction of body mass, is ϳ10-fold lower in mice than in humans (12, 13), whereas the corresponding values for liver glycogen are comparable (14). Thus, the relative role of these two glycogen storage depots may be different between the two species. The relative importance of muscle and liver glycogen stores as fuel sources for exercise has been studied extensively in rats (15-17). Exhaustive exercise either by treadmill running or swimming resulted in a reduction of muscle glycogen by 70 or Ͼ90%, respectively (15, 16). Both exercise methods reduced liver glycogen Ͼ90%. Using less strenuous exercise regimens, muscle g...

show abstract

Section: Discussionmentioning

confidence: 99%

Exercise Capacity of Mice Genetically Lacking Muscle Glycogen Synthase

Pederson

Cope

Schroeder

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The IL-6 response to exercise has recently been reviewed (Pedersen and Hoffman-Goetz 2000;Pedersen et al 2001Pedersen et al , 2003aFebbraio and Pedersen 2002). In short, a marked increase in circulating levels of IL-6 after exercise without muscle damage has been a remarkably consistent finding.…”

Section: Effect Of Exercisementioning

confidence: 98%

“…Thus, skeletal muscle has the capacity to express, for example, interleukin (IL)-6, IL-8, and IL-15 Chan et al 2004), and muscle contractions play a regulatory role in the muscular expression of these cytokines. Solid evidence exists that IL-6 Pedersen 2002, 2005;Pedersen et al 2003aPedersen et al , 2003b and IL-8 (Nieman et al 2003;Chan et al 2004;Akerstrom et al 2005) are regulated by concentric muscle contractions, both at the messenger ribonucleic acid (mRNA) and the protein levels, and a recent study demonstrates that strength training regulates the expression of IL-15. A bout of exercise provokes the appearance of several cytokines in the circulation, including IL-6, IL-1 receptor antagonist, IL-8, and IL-10, whereas tumour necrosis factor (TNF) is only stimulated by very intense exercise.…”

Section: Introductionmentioning

confidence: 99%

The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15

Nielsen

Pedersen

2007

Appl. Physiol. Nutr. Metab.

176

116

View full text Add to dashboard Cite

Skeletal muscle fibers express several cytokines, including interleukin (IL)-6, IL-8, and IL-15. Solid evidence exists that muscular IL-6 and IL-8 are regulated by muscle contractions, at both the mRNA and the protein levels. IL-6 increases insulin-stimulated glucose disposal and fatty acid oxidation in humans in vivo. Both IL-6 and IL-8 are released from working skeletal muscle, but because IL-6 contributes to the systemic circulation only a small transient net release of IL-8 is found from working muscle, suggesting that IL-8 may exert its effects locally in the muscle. IL-15 is a recently discovered growth factor, which is highly expressed in skeletal muscle. Interestingly, although IL-15 has been demonstrated as having anabolic effects on skeletal muscle in vitro and in vivo, it seems to play a role in reducing adipose tissue mass, and a role for IL-15 in muscle-fat cross-talk has been hypothesized. In conclusion, muscle-derived cytokines appear to have important roles in metabolism, and exercise plays a role in orchestrating the interplay between cytokines and metabolism.

show abstract

“…It has been reported that lipid levels are changed under inflammatory conditions [46]. Studies demonstrated that IL-6 and TNF-α are involved in the increase in the circulating level of free fatty acids and contribute to the elevation of serum lipids (cholesterol and triglyceride) and triglyceride in the liver [46,47,48,49]. These data could explain that the pretreatment of animals with anti-IL-6 or anti-TNF-α prior to KTX 2 injection improved insulin sensitivity and, consequently, decreased carbohydrate and lipid disorders compared to the group injected with KTX 2 .…”

Section: Discussionmentioning

confidence: 99%

Systemic Responses following Brain Injuries and Inflammatory Process Activation Induced by a Neurotoxin of <b><i>Androctonus</i></b> Scorpion Venom

Taibi-Djennah

Matin-Eauclaire²,

Laraba-Djebari³

2015

Neuroimmunomodulation

View full text Add to dashboard Cite

Objective: Kaliotoxin 2 (KTX₂), a neurotoxin isolated from Androctonus australis hector scorpion venom, presents a high affinity with the voltage-gated potassium channels. The targets of KTX₂ in the brain and its toxic effects on the cerebral cortex have been extensively studied; however, its deleterious systemic effects on other organ systems have not yet been investigated. Inflammatory response induced by KTX₂ is supported by cytokine release which could provoke multiple organ dysfunction and diverse biological disorders in mammals. The possibility that inflammatory response and brain injuries induced by KTX₂ may lead to functional disturbances, e.g. in the pancreas and the liver, were investigated. The contribution of IL-6 and TNF-α to the modulation of pathophysiological effects induced by KTX₂ was also tested. Methods: NMRI mice were injected by the intracerebroventricular route with a sublethal dose of KTX₂ or saline solution. Inflammatory response and oxidative stress were assessed in sera and tissue homogenates. Biomarkers of pancreatic and hepatic functions and the correlation with tissue damage in the brain, liver and pancreas were also analyzed. Results: The obtained results revealed that KTX₂ injection induced an inflammatory process activation and imbalanced redox status. It also induced severe alterations in cerebral cortex, hepatic and pancreatic tissues associated with a significant increase in pancreatic and hepatic pathological biomarkers. Cytokine antagonists injected 30 min prior to KTX₂ led to a significant reduction of all disturbances induced by KTX₂. Conclusion: In addition to its significant toxicity on the central nervous system, KTX₂ can also affect pancreatic and hepatic functions, probably by an indirect mechanism involving activation of the inflammatory response with release of IL-6 and TNF-α.

show abstract

Untitled

Cited by 421 publications

References 86 publications

Exercise Capacity of Mice Genetically Lacking Muscle Glycogen Synthase

Exercise Capacity of Mice Genetically Lacking Muscle Glycogen Synthase

The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15

Systemic Responses following Brain Injuries and Inflammatory Process Activation Induced by a Neurotoxin of <b><i>Androctonus</i></b> Scorpion Venom

Contact Info

Product

Resources

About