IL-6 signalling in exercise and disease

2007 ◽  
Vol 35 (5) ◽  
pp. 1295-1297 ◽  
Author(s):  
B.K. Pedersen
Keyword(s):  
Type 2 Diabetes ◽  
Dominant Negative ◽  
Metabolic Effects ◽  
Glucose Disposal ◽  
Acid Oxidation ◽  
Low Grade ◽  
Healthy Humans ◽  
Multinucleated Cells ◽  
Anti Inflammatory

Low-grade chronic inflammation is a feature of Type 2 diabetes and appears to play a pathogenetic role in insulin resistance. It is well known that cytokines, besides their immunoregulatory roles, are important players in metabolism. Moreover, it has become evident that skeletal muscles express several cytokines, which belong to distinct cytokine classes. IL-6 (interleukin-6) is a pleiotropic cytokine produced by virtually all multinucleated cells including skeletal myocytes where it is produced in response to contraction. IL-6 is subsequently released into the circulation, where it works in a hormone-like fashion to induce lipolysis and fat oxidation. In more recent experiments, it has been shown that IL-6 infusion increases glucose disposal during a hyperinsulinaemic euglycaemic clamp in healthy humans. IL-6 treatment of myotubes increases fatty acid oxidation, basal and insulin-stimulated glucose uptake and translocation of GLUT4 to the plasma membrane. Furthermore, IL-6 rapidly and markedly increases AMPK (AMP-activated protein kinase) and the metabolic effects of IL-6 were abrogated in AMPK dominant negative-infected cells. Finally, IL-6 mediates anti-inflammatory effects by stimulating the production of anti-inflammatory cytokines and by suppressing TNFα (tumour necrosis factor α) production. We suggest that IL-6 and other muscle-derived cytokines (myokines) may play a role in defending Type 2 diabetes.

The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control

2006 ◽  
Vol 42 ◽  
pp. 105-117 ◽  
Author(s):  
Bente Klarlund Pedersen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Chronic Diseases ◽  
The Body ◽  
Muscle Fibres ◽  
Low Grade ◽  
Regular Exercise ◽  
Anti Inflammatory

Chronic low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease and type 2 diabetes. Regular exercise offers protection against all-cause mortality, primarily by protection against atherosclerosis and insulin resistance and there is evidence that physical training is effective as a treatment in patients with chronic heart diseases and type 2 diabetes. Regular exercise induces anti-inflammatory actions. During exercise, IL-6 (interleukin-6) is produced by muscle fibres. IL-6 stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra (interleukin-1 receptor antagonist) and IL-10 (interleukin-10) and inhibits the production of the pro-inflammatory cytokine TNF-a (tumour necrosis factor-a). In addition, IL-6 enhances lipid turnover, stimulating lipolysis as well as fat oxidation. It is suggested that regular exercise induces suppression of TNF-a and thereby offers protection against TNF-a-induced insulin resistance. Recently, IL-6 was introduced as the first myokine, defined as a cytokine, that is produced and released by contracting skeletal muscle fibres, exerting its effects in other organs of the body. Myokines may be involved in mediating the beneficial health effects against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.

Lifestyle Measures to Reduce Inflammation

2011 ◽  
Vol 6 (1) ◽  
pp. 4-13 ◽  
Author(s):  
Glenn A. Gaesser ◽  
Siddhartha S. Angadi ◽  
Dana M. Ryan ◽  
Carol S. Johnston
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Aerobic Exercise ◽  
Inflammatory Markers ◽  
Dietary Factors ◽  
Low Grade ◽  
Inflammatory Status ◽  
Anti Inflammatory ◽  
Low Grade Inflammation

Chronic low-grade inflammation associated with cardiovascular disease and type 2 diabetes (T2D) may be ameliorated with exercise and/or diet. High levels of physical activity and/or cardiorespiratory fitness are associated with reduced risk of low-grade inflammation. Both aerobic and resistance exercise have been found to improve inflammatory status, with the majority of evidence suggesting that aerobic exercise may have broader anti-inflammatory effects. In particular, aerobic exercise appears to improve the balance between pro- and anti-inflammatory markers. Improvement in inflammatory status is most likely to occur in persons with elevated levels of pro-inflammatory markers prior to intervention. A number of dietary factors, including fiber-rich foods, whole grains, fruits (especially berries), omega-3 fatty acids, antioxidant vitamins (eg, C and E), and certain trace minerals (eg, zinc) have been documented to reduce blood concentrations of inflammatory markers. Anti-inflammatory foods may also help mitigate the pro-inflammatory postprandial state that is particularly evident after ingestion of meals high in saturated fat. Intensive lifestyle interventions involving both exercise and diet appear to be most effective. For the most part, anti-inflammatory effects of exercise and diet are independent of weight loss. Thus overweight and obese men and women, who are most likely to have a pro-inflammatory profile, do not necessarily have to normalize body mass index to improve inflammatory status and reduce risk of type 2 diabetes and cardiovascular disease.

scholarly journals An Anti-Inflammatory Sterol Decreases Obesity-Related Inflammation-Induced Insulin Resistance and Metabolic Dysregulation

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Chris L. Reading ◽  
Jaime Flores-Riveros ◽  
Dwight R. Stickney ◽  
James M. Frincke
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Laboratory Data ◽  
Low Grade ◽  
Insulin Sensitizer ◽  
Monocyte Chemoattractant Protein 1 ◽  
Metabolic Dysregulation ◽  
Treatment Naïve ◽  
Anti Inflammatory

Obesity-related inflammation-induced insulin resistance and metabolic dysregulation were investigated in retrospective analysis of placebo hematologic and metabolic laboratory data from trials associated with increasing chronic low-grade inflammation and body mass index. Studies included healthy subjects and those with progressive stages of metabolic dysregulation, including type 2 diabetes mellitus with uncontrolled hemoglobin A1c. Intrasubject variances in erythroid and metabolic values increased with metabolic dysregulation. Random effects were demonstrated in treatment-naïve diabetes for erythroid, glucose, and HbA1c fluctuations. The anti-inflammatory insulin sensitizer, HE3286, was tested for its ability to decrease obesity-related inflammation-induced insulin resistance and metabolic dysregulation in diabetes. HE3286 significantly decreased erythroid and metabolic variances and improved 1,5-anhydroglucitol (a surrogate of postprandial glucose) compared to the placebo group. HE3286 HbA1c decrease correlated with weight loss and inversely with baseline monocyte chemoattractant protein-1 (MCP-1) in metformin-treated diabetics. Normalization of HbA1c to the 84-day average hemoglobin revealed that HE3286 HbA1c decrease correlated with high baseline MCP-1 and MCP-1 decrease in treatment-naïve diabetics. HE3286 decreased insulin resistance, increased the frequency of decreased day 84 HbA1c in metformin-treated subjects, and decreased day 112 HbA1c in treatment-naïve diabetics. HE3286 may be useful to restore metabolic homeostasis in type 2 diabetes.

scholarly journals The Role of Transforming Growth Factor-Beta in Diabetic Nephropathy

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Karina Braga Gomes ◽  
Kathryna Fontana Rodrigues ◽  
Ana Paula Fernandes
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Low Grade ◽  
Anti Inflammatory

Several studies have demonstrated that chronic and low-grade inflammation is closely linked to type 2 diabetes mellitus. The associated mechanisms are related to synthesis and release of proinflammatory and anti-inflammatory cytokines, mainly by the adipose tissue. Moreover, there are evidences that cytokines and adhesion molecules are important for development of diabetic nephropathy. Among the cytokines associated with inflammatory responses in type 2 diabetes mellitus, the transforming growth factor-β (TGF-β) has been recognized as a central player in the diabetic nephropathy being involved in the development of glomerulosclerosis and interstitial fibrosis, as observed in the course of end-stage renal disease. Although TGF-β1 is classically an anti-inflammatory immune mediator it has been shown that in the presence of IL-6, which increases before the onset of T2D, TGF-β1 favors the differentiation of T helper 17 (Th17) cells that are activated in many pro-inflammatory conditions. Since TGF-β1 mRNA and consequently serum TGF-β1 levels are under genetic control, this review aims to discuss the relationship of TGF-β1 levels and polymorphisms in the development of nephropathy in type 2 diabetes mellitus.

scholarly journals Anti-Inflammatory Strategies Targeting Metaflammation in Type 2 Diabetes

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2224 ◽  
Author(s):  
Alina Kuryłowicz ◽  
Krzysztof Koźniewski
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Low Grade ◽  
Peripheral Tissues ◽  
Inflammatory State ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Immunomodulatory Therapies

One of the concepts explaining the coincidence of obesity and type 2 diabetes (T2D) is the metaflammation theory. This chronic, low-grade inflammatory state originating from metabolic cells in response to excess nutrients, contributes to the development of T2D by increasing insulin resistance in peripheral tissues (mainly in the liver, muscles, and adipose tissue) and by targeting pancreatic islets and in this way impairing insulin secretion. Given the role of this not related to infection inflammation in the development of both: insulin resistance and insulitis, anti-inflammatory strategies could be helpful not only to control T2D symptoms but also to treat its causes. This review presents current concepts regarding the role of metaflammation in the development of T2D in obese individuals as well as data concerning possible application of different anti-inflammatory strategies (including lifestyle interventions, the extra-glycemic potential of classical antidiabetic compounds, nonsteroidal anti-inflammatory drugs, immunomodulatory therapies, and bariatric surgery) in the management of T2D.

scholarly journals The anti-inflammatory function of HDL is impaired in type 2 diabetes: role of hyperglycemia, paraoxonase-1 and low grade inflammation

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Sanam Ebtehaj ◽  
Eke G. Gruppen ◽  
Mojtaba Parvizi ◽  
Uwe J. F. Tietge ◽  
Robin P. F. Dullaart
Keyword(s):  
Type 2 Diabetes ◽  
Paraoxonase 1 ◽  
Low Grade ◽  
Anti Inflammatory ◽  
Low Grade Inflammation

scholarly journals Muscle-Specific Overexpression of CD36 Reverses the Insulin Resistance and Diabetes of MKR Mice

Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4667-4676 ◽  
Author(s):  
Lisa Héron-Milhavet ◽  
Martin Haluzik ◽  
Shoshana Yakar ◽  
Oksana Gavrilova ◽  
Stephanie Pack ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Cell Function ◽  
Dominant Negative ◽  
Whole Body ◽  
Acid Oxidation

Abstract Insulin resistance is one of the primary characteristics of type 2 diabetes. Mice overexpressing a dominant-negative IGF-I receptor specifically in muscle (MKR mice) demonstrate severe insulin resistance with high levels of serum and tissue lipids and eventually develop type 2 diabetes at 5–6 wk of age. To determine whether lipotoxicity plays a role in the progression of the disease, we crossed MKR mice with mice overexpressing a fatty acid translocase, CD36, in skeletal muscle. The double-transgenic MKR/CD36 mice showed normalization of the hyperglycemia and the hyperinsulinemia as well as a marked improvement in liver insulin sensitivity. The MKR/CD36 mice also exhibited normal rates of fatty acid oxidation in skeletal muscle when compared with the decreased rate of fatty acid oxidation in MKR. With the reduction in insulin resistance, β-cell function returned to normal. These and other results suggest that the insulin resistance in the MKR mice is associated with increased muscle triglycerides levels and that whole-body insulin resistance can be, at least partially, reversed in association with a reduction in muscle triglycerides levels, although the mechanisms are yet to be determined.

Novel anti-diabetic effect of SCM-198 via inhibiting the hepatic NF-κB pathway in db/db mice

2011 ◽  
Vol 32 (2) ◽  
pp. 185-195 ◽  
Author(s):  
Hui Huang ◽  
Hong Xin ◽  
Xinhua Liu ◽  
Yajun Xu ◽  
Danyi Wen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fasting Blood Glucose ◽  
Cholesterol Concentration ◽  
Low Grade ◽  
Plasma Insulin Concentration ◽  
Iκb Kinase ◽  
Anti Inflammatory

There are reports of early evidence that suggest the involvement of chronic low-grade inflammation in the pathogenesis of Type 2 diabetes. Thus, substances that have effects in reducing inflammation could be potential drugs for Type 2 diabetes. Leonurine (4-guanidino-n-butyl syringate; SCM-198) is an alkaloid in HL (Herba leonuri), which was reported to possess anti-inflammatory properties. We hypothesize that SCM-198 may have beneficial effects on Type 2 diabetes. In the present study, we attempted to test this hypothesis by evaluating the anti-diabetic effect of SCM-198 and the possible underlying mechanisms of its effects in db/db mice. SCM-198 (50, 100 and 200 mg/kg of body weight), pioglitazone (50 mg/kg of body weight, as a positive control) or 1% CMC-Na (sodium carboxymethylcellulose) were administered to the db/db or db/m mice once daily for 3 weeks. After 3 weeks, SCM-198 (200 mg/kg of body weight) treatment significantly reduced the fasting blood glucose level and increased the plasma insulin concentration in the db/db mice, meanwhile it significantly lowered the plasma TAG (triacylglycerol) concentration and increased the HDL (high-density lipoprotein)-cholesterol concentration. Moreover, the dysregulated transcription of the hepatic glucose metabolic enzymes, including GK (glucokinase), G6Pase (glucose-6-phosphatase) and PEPCK (phosphoenolpyruvate carboxykinase), was recovered by an Akt-dependent pathway. The pro-inflammatory mediators {such as TNFα (tumour necrosis factor α), IL (interleukin)-6, IL-1β, degradation of IκB [inhibitor of NF-κB (nuclear factor-κB)] α and thereafter activation of NF-κB} were reversed by SCM-198 treatment in the db/db mice. The present study provides first evidence that SCM-198 exhibits anti-inflammatory activity and has an ameliorating effect on diabetic symptoms via inhibiting of NF-κB/IKK (IκB kinase) pathway. Consequently, we suggest that SCM-198 may be a prospective agent for prevention and/or moderation of the progress of Type 2 diabetes.

scholarly journals Therapeutic Effects of Quercetin on Inflammation, Obesity, and Type 2 Diabetes

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Shuang Chen ◽  
Hongmei Jiang ◽  
Xiaosong Wu ◽  
Jun Fang
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Capillary Permeability ◽  
Therapeutic Effects ◽  
Low Grade ◽  
Beneficial Effects ◽  
Anti Inflammatory ◽  
Low Grade Inflammation

In previous studies, abdominal obesity has been related to total low-grade inflammation and in some cases has resulted in insulin resistance and other metabolism related disorders such as diabetes. Quercetin is a polyphenol, which is a derivative of plants, and has been shownin vitroas well as in a few animal models to have several potential anti-inflammatory as well as anticarcinogenic applications. The substance has also been shown to aid in the attenuation of lipid peroxidation, platelet aggregation, and capillary permeability. However, further research is called for to gain a better understanding of how quercetin is able to provide these beneficial effects. This manuscript reviewed quercetin’s anti-inflammatory properties in relation to obesity and type 2 diabetes.

scholarly journals Leptin Improves Insulin Resistance and Hyperglycemia in a Mouse Model of Type 2 Diabetes

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 4024-4035 ◽  
Author(s):  
Yuka Toyoshima ◽  
Oksana Gavrilova ◽  
Shoshana Yakar ◽  
William Jou ◽  
Stephanie Pack ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Insulin Receptors ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Primary Defect ◽  
Peripheral Tissues ◽  
Liver And Pancreas ◽  
Insulin Responsiveness

Abstract Leptin has metabolic effects on peripheral tissues including muscle, liver, and pancreas, and it has been successfully used to treat lipodystrophic diabetes, a leptin-deficient state. To study whether leptin therapy can be used for treatment of more common cases of type 2 diabetes, we used a mouse model of type 2 diabetes (MKR mice) that show normal leptin levels and are diabetic due to a primary defect in both IGF-I and insulin receptors signaling in skeletal muscle. Here we show that leptin administration to the MKR mice resulted in improvement of diabetes, an effect that was independent of the reduced food intake. The main effect of leptin therapy was enhanced hepatic insulin responsiveness possibly through decreasing gluconeogenesis. In addition, the reduction of lipid stores in liver and muscle induced by enhancing fatty acid oxidation and inhibiting lipogenesis led to an improvement of the lipotoxic condition. Our data suggest that leptin could be a potent antidiabetic drug in cases of type 2 diabetes that are not leptin resistant.

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