Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6

2008 ◽  
Vol 88 (4) ◽  
pp. 1379-1406 ◽  
Author(s):  
Bente K. Pedersen ◽  
Mark A. Febbraio
Keyword(s):  
Skeletal Muscle ◽  
Interleukin 6 ◽  
Skeletal Muscles ◽  
Insulin Action ◽  
Endocrine Effects ◽  
Endocrine Organ ◽  
Metabolic Role ◽  
Gp130 Receptor ◽  
Health And Disease

Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as “myokines.” Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.

Role of myokines in exercise and metabolism

2007 ◽  
Vol 103 (3) ◽  
pp. 1093-1098 ◽  
Author(s):  
Bente Klarlund Pedersen ◽  
Thorbjörn C. A. Åkerström ◽  
Anders R. Nielsen ◽  
Christian P. Fischer
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Contractile Activity ◽  
Endocrine Effects ◽  
Skeletal Muscle Function ◽  
The Past ◽  
Exercise Induced ◽  
Immune Changes ◽  
Muscle Contractile

During the past 20 yr, it has been well documented that exercise has a profound effect on the immune system. With the discovery that exercise provokes an increase in a number of cytokines, a possible link between skeletal muscle contractile activity and immune changes was established. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an “exercise factor,” which could mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We suggest that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either paracrine or endocrine effects should be classified as “myokines.” Since the discovery of interleukin (IL)-6 release from contracting skeletal muscle, evidence has accumulated that supports an effect of IL-6 on metabolism. We suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines should be named “myokines.” Interestingly, recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. Thus skeletal muscle has the capacity to express several myokines. To date the list includes IL-6, IL-8, and IL-15, and contractile activity plays a role in regulating the expression of these cytokines in skeletal muscle. The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines.

scholarly journals Force Transmission between Synergistic Skeletal Muscles through Connective Tissue Linkages

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Huub Maas ◽  
Thomas G. Sandercock
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Safety Net ◽  
Force Transmission ◽  
Connective Tissues ◽  
Future Studies ◽  
Myofascial Force Transmission ◽  
In Series ◽  
Health And Disease

The classic view of skeletal muscle is that force is generated within its muscle fibers and then directly transmitted in-series, usually via tendon, onto the skeleton. In contrast, recent results suggest that muscles are mechanically connected to surrounding structures and cannot be considered as independent actuators. This article will review experiments on mechanical interactions between muscles mediated by such epimuscular myofascial force transmission in physiological and pathological muscle conditions. In a reduced preparation, involving supraphysiological muscle conditions, it is shown that connective tissues surrounding muscles are capable of transmitting substantial force. In more physiologically relevant conditions of intact muscles, however, it appears that the role of this myofascial pathway is small. In addition, it is hypothesized that connective tissues can serve as a safety net for traumatic events in muscle or tendon. Future studies are needed to investigate the importance of intermuscular force transmission during movement in health and disease.

Effect of diltiazem on skeletal muscle 3-O-methylglucose transport in bacteremic rats

1989 ◽  
Vol 256 (3) ◽  
pp. R716-R721
Author(s):  
M. V. Westfall ◽  
M. M. Sayeed
Keyword(s):  
Escherichia Coli ◽  
Skeletal Muscle ◽  
Low Temperature ◽  
Skeletal Muscles ◽  
Cytochalasin B ◽  
Sugar Transport ◽  
Male Rats ◽  
Saline Control ◽  
Permeability Changes

This study examined whether alterations in cellular Ca2+ regulation contribute to previously observed changes in skeletal muscle sugar transport during bacteremia. Fasted male rats received saline (control) or bacteria (4 X 10(10) Escherichia coli/kg) intraperitoneally. Twelve hours later, basal and insulin-mediated 3-O-methylglucose (3MG) transport was measured in isolated soleus muscles. Measurements of 3MG transport in the presence of cytochalasin b or at a low temperature (0.5 degree C) indicated that altered sugar transport in bacteremic rat muscles was not due to nonspecific membrane permeability changes. To determine the role of Ca2+ in the pathogenesis of altered sugar transport during bacteremia, rats were treated with the Ca2+ antagonist diltiazem (DZ, 0.6-2.4 mg/kg) at various times (0, 0 + 7.5, 10 h) after saline or bacterial injection. In bacteremic rats given 2.4 mg/kg DZ at 10 h, basal and insulin-mediated transport were similar to control values. This dose of DZ had little effect on control muscles. The addition of 20 microM DZ to the incubation media did not affect basal or insulin-mediated 3MG transport in bacteremic rat muscles. Addition of the Ca2+ agonist BAY K 8644 to the incubation media had no effect on sugar transport in bacteremic rat muscles but caused alterations in control rat muscles that were comparable to those observed in bacteremia. These results suggest that alterations in Ca2+ regulation could contribute to the previously observed changes in sugar transport in skeletal muscles from bacteremic rats.

Inhibitors such as staurosporine, H-7 or polymyxin B cannot be used in skeletal muscle to prove the role of protein kinase C on insulin action

1992 ◽  
Vol 12 (5) ◽  
pp. 413-424 ◽  
Author(s):  
Anna Gumà ◽  
Purificación Muñoz ◽  
Marta Camps ◽  
Xavier Testar ◽  
Manuel Palacín ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Action ◽  
Lactate Production ◽  
Polymyxin B ◽  
Transport Activity ◽  
System A ◽  
Kinase C

The precise role of protein kinase C in insulin action in skeletal muscle is not well defined. Based on the fact that inhibitors of protein kinase C block some insulin effects, it has been concluded that some of the biological actions of insulin are mediated via protein kinase C. In this study, we present evidence that inhibitors of protein kinase C such as staurosporine, H-7 or polymyxin B cannot be used to ascertain the role of protein kinase C in skeletal muscle. This is based on the following experimental evidences: a) staurosporine, H-7 and polymyxin B markedly block in muscle the effect of insulin on System A transport activity; however, this effect of insulin is not mimicked in muscle by TPA-induced stimulation of protein kinase C, b) H-7 and polymyxin B block insulin action on System A transport activity in an additive manner to the inhibitory effect of phorbol esters, c) staurosporine, H-7 and polymyxin B block the effect of insulin on lactate production, a process that is activated by insulin and TPA in an additive fashion, and d) staurosporine completely blocks the tyrosine kinase activity of insulin receptors partially purified from rat skeletal muscle.

Role of Interleukin-6 in Skeletal Muscle Protein Breakdown and Cathepsin Activity in vivo

1996 ◽  
Vol 28 (5) ◽  
pp. 361-366 ◽  
Author(s):  
J. Fujita ◽  
T. Tsujinaka ◽  
C. Ebisui ◽  
M. Yano ◽  
H. Shiozaki ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Interleukin 6 ◽  
Muscle Protein ◽  
Protein Breakdown ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Breakdown ◽  
Cathepsin Activity

scholarly journals Histone deacetylase 5 regulates interleukin 6 secretion and insulin action in skeletal muscle

2020 ◽  
Vol 42 ◽  
pp. 101062
Author(s):  
Oleksiy Klymenko ◽  
Tim Brecklinghaus ◽  
Matthias Dille ◽  
Christian Springer ◽  
Christian de Wendt ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Histone Deacetylase ◽  
Interleukin 6 ◽  
Insulin Action

scholarly journals Skeletal Muscle Na,K-ATPase as a Target for Circulating Ouabain

2020 ◽  
Vol 21 (8) ◽  
pp. 2875 ◽  
Author(s):  
Violetta V. Kravtsova ◽  
Elena V. Bouzinova ◽  
Vladimir V. Matchkov ◽  
Igor I. Krivoi
Keyword(s):  
Skeletal Muscle ◽  
Diaphragm Muscle ◽  
Hindlimb Suspension ◽  
Resting Potential ◽  
Human Red Blood Cells ◽  
Central Nervous Systems ◽  
Health And Disease ◽  
Specific Increase ◽  
20 Nm

While the role of circulating ouabain-like compounds in the cardiovascular and central nervous systems, kidney and other tissues in health and disease is well documented, little is known about its effects in skeletal muscle. In this study, rats were intraperitoneally injected with ouabain (0.1–10 µg/kg for 4 days) alone or with subsequent injections of lipopolysaccharide (1 mg/kg). Some rats were also subjected to disuse for 6 h by hindlimb suspension. In the diaphragm muscle, chronic ouabain (1 µg/kg) hyperpolarized resting potential of extrajunctional membrane due to specific increase in electrogenic transport activity of the α2 Na,K-ATPase isozyme and without changes in α1 and α2 Na,K-ATPase protein content. Ouabain (10–20 nM), acutely applied to isolated intact diaphragm muscle from not injected rats, hyperpolarized the membrane to a similar extent. Chronic ouabain administration prevented lipopolysaccharide-induced (diaphragm muscle) or disuse-induced (soleus muscle) depolarization of the extrajunctional membrane. No stimulation of the α1 Na,K-ATPase activity in human red blood cells, purified lamb kidney and Torpedo membrane preparations by low ouabain concentrations was observed. Our results suggest that skeletal muscle electrogenesis is subjected to regulation by circulating ouabain via the α2 Na,K-ATPase isozyme that could be important for adaptation of this tissue to functional impairment.

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