Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well known that obesity is associated with insulin resistance and an increased risk for type 2 diabetes mellitus. Formerly it was postulated that increased lipolysis and consequently free fatty acid (FFA) production, from with triglycerides overloaded fat cells, would disrupt glucose homeostasis via Randle's hypothesis. Lipodystrophy, however, also leads to insulin resistance. Recently it has become clear that adipose tissue functions as an endocrine organ and secretes numerous proteins in response to a variety of stimuli. These secreted proteins exert a pleiotropic effect. The proteins that are involved in glucose and fat metabolism and hence can influence insulin resistance are discussed in this paper. They include leptin, resistin, adiponectin, acylation-stimulating protein, tumour necrosis factor-alpha and interleukin-6. The stimuli for production and the site and mechanism of action in relation to insulin resistance will be discussed. None of these proteins are, however, without controversy with regard to their mechanism of action. Furthermore, some of these proteins may influence each other via common signalling pathways. A theory is presented to link the interrelationship between these adipocyte secretory products and their effect on insulin resistance.
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PMID:Adipose tissue as an endocrine organ: impact on insulin resistance. 1294 64

It has long been known that obesity and insulin resistance are linked. Recently, it has been shown that adipocytes secrete several proteins including tumour necrosis factor-alpha, interleukin-6, resistin, and adiponectin. Since several of these so-called adipocytokines influence insulin sensitivity and glucose metabolism profoundly, they might provide a molecular link between increased adiposity and impaired insulin sensitivity. Thiazolidinediones which decrease insulin resistance and are used in the treatment of Type 2 diabetes seem to mediate part of their insulin-sensitising effects via modulation of adipocytokine expression. Furthermore, hormones such as beta-adrenergic agonists, insulin, glucocorticoids, and growth hormone might impair insulin sensitivity at least in part via up-regulation or down-regulation of adipocytokine synthesis. We summarise the current knowledge on how major adipocyte-secreted proteins are regulated by hormones and drugs influencing insulin sensitivity and discuss its implications for insulin resistance and obesity.
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PMID:Regulation of adipocytokines and insulin resistance. 1460 6

I investigated whether metabolism of essential fatty acids and the concentrations of their long-chain metabolites (long-chain polyunsaturated fatty acids [LCPUFAs]) are altered in fetal or perinatal growth retardation, maternal hypercholesterolemia, low-grade systemic inflammation, insulin resistance, and atherosclerosis, conditions that predispose to the development of coronary heart disease (CHD).I critically reviewed the literature pertaining to the metabolism of essential fatty acids in CHD and conditions that predispose to it.LCPUFAs enhance endothelial nitric oxide synthesis, suppress the production of the proinflammatory cytokines tumor necrosis factor and interleukin-6, attenuate insulin resistance, and have antiatherosclerotic properties. Low-birthweight infants have decreased concentrations of LCPUFAs, especially arachidonic acid. Neonatal arachidonic acid status is related to intrauterine growth, and LCPUFAs improve fetal and postnatal growth. LCPUFAs are useful in the management of hyperlipidemia, inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, and may mediate the beneficial actions of statins. Plasma concentrations of various LCPUFAs are low in diabetes mellitus, hypertension, and CHD and in populations at high risk of CHD. Breast milk is rich in LCPUFAs, and this may explain why and how adequate (6 mo to 1 y) breast feeding protects against the development of obesity, hypertension, insulin resistance, and CHD.LCPUFAs are essential for the growth and development of the fetus and infant. LCPUFAs can prevent various conditions that predispose to the development of CHD. The low incidence of CHD seen in adequately breast-fed infants can be linked to the LCPUFA content of breast milk. Based on this evidence, I suggest that provision of LCPUFAs during critical periods of growth, especially from the second trimester of pregnancy to age 5 y, prevents CHD in adult life.
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PMID:A perinatal strategy to prevent coronary heart disease. 1462 57

It is now recognized that the WAT (white adipose tissue) produces a variety of bioactive peptides, collectively termed "adipokines". Alteration of WAT mass in obesity or lipoatrophy affects the production of most adipose secreted factors. Since both conditions are associated with insulin resistance, the idea has emerged that certain adipokines might influence insulin action. Among these, tumour necrosis factor alpha, interleukin-6 and resistin are increased in the obese state and interfere negatively with insulin-mediated processes. Conversely, leptin and adiponectin exert an insulin-sensitizing effect, at least in part by favouring tissue fatty-acid oxidation through AMP-activated kinase activation. Obesity-induced insulin resistance has been linked to leptin resistance and decreased plasma adiponectin, while administration of leptin and adiponectin normalizes plasma levels in lipoatrophic mice and reverses insulin resistance. Thiazolidinedione anti-diabetic agents increase endogenous adiponectin production in rodents and humans, supporting the idea that drugs targeting adipokines might represent a new therapeutic approach to sensitize peripheral tissues to insulin.
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PMID:Extending the glucose/fatty acid cycle: a glucose/adipose tissue cycle. 1464 Oct 17

The prevalence of overweight and obesity continues to increase rapidly in the United States, with more than half of all adults currently overweight or obese. In general, people become obese because of a combination of inherited genes and a lifestyle consisting of low levels of physical activity and consumption of excess calories. Obesity, especially the central or visceral type, is a predisposing factor for the development of type 2 diabetes mellitus, hypertension, and cardiovascular disease (CVD). Obesity and type 2 diabetes are associated with insulin resistance. The relation among obesity, insulin resistance, and CVD appears to develop at a relatively young age. Central obesity is linked with hyperinsulinemia, insulin resistance, dyslipidemia, and proinflammatory and prothrombotic clinical states. Adipose tissue synthesizes and secretes biologically active molecules that may affect CVD risk factors. These chemical messengers include adiponectin, resistin, leptin, plasminogen activator inhibitor-1, tumor necrosis factor-alpha, and interleukin-6. In overweight and obese individuals, weight loss may improve insulin sensitivity, leading to reduction in risk factors for CVD and, consequently, the potential for cardiovascular events. Agents that improve insulin sensitivity, such as the thiazolidinediones, have been shown to reduce visceral obesity. Decreases in visceral adipose tissue contribute to improvements in insulin sensitivity and blood pressure, and weight loss reduces serum levels of triglycerides and low-density lipoprotein cholesterol while increasing serum levels of high-density lipoprotein cholesterol. Reduction of risk factors suggests that the development of cardiovascular disease will be reduced by the improvement of insulin sensitivity and weight loss.
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PMID:Obesity as a cardiovascular risk factor. 1467 64

Metabolic and nutritional derangements are prominent features of the uremic syndrome. Recent evidence suggest that several large-molecular-weight molecules that often are elevated in uremia, such as leptin, ghrelin, and proinflammatory cytokines, may have nutritional impact in this patient group. On the basis of present knowledge, these compounds could be regarded as suspected but not established uremic toxins. The discovery of the ob gene, its product leptin, and cerebral leptin receptors has undoubtedly widened our understanding of obesity and the underlying molecular and physiologic mechanisms that regulate food intake and body weight. Moreover, the recent discovery of leptin receptor isoforms in several peripheral organs suggests that leptin besides having a central function also has several important peripheral biological functions. Because uremic patients in general have an inappropriate elevation of circulatory leptin, further research is necessary to determine the potential biological effects of elevated leptin levels in end-stage renal disease. Also, because many symptoms and findings prevalent in the uremic syndrome are known to be associated with elevated levels of proinflammatory cytokines, such as interleukin-6, future studies are needed to evaluate the role of specific anti-inflammatory treatment strategies in malnourished uremic patients.
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PMID:Leptin, ghrelin, and proinflammatory cytokines: compounds with nutritional impact in chronic kidney disease? 1468 62

Recent data have revealed that the plasma concentration of inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), is increased in the insulin resistant states of obesity and type 2 diabetes, raising questions about the mechanisms underlying inflammation in these two conditions. It is also intriguing that an increase in inflammatory mediators or indices predicts the future development of obesity and diabetes. Two mechanisms might be involved in the pathogenesis of inflammation. Firstly, glucose and macronutrient intake causes oxidative stress and inflammatory changes. Chronic overnutrition (obesity) might thus be a proinflammatory state with oxidative stress. Secondly, the increased concentrations of TNF-alpha and IL-6, associated with obesity and type 2 diabetes, might interfere with insulin action by suppressing insulin signal transduction. This might interfere with the anti-inflammatory effect of insulin, which in turn might promote inflammation.
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PMID:Inflammation: the link between insulin resistance, obesity and diabetes. 1469 76

Insulin resistance, both in nondiabetic and diabetic subjects, is frequently associated with obesity, particularly an excess of central fat. Many of the features that have been ascribed to the metabolic or insulin-resistance syndrome are also more commonly found in obese subjects. These phenotypes include diabetic dyslipidaemia, elevation of levels of plasminogen activator inhibitor-1, microalbuminuria and endothelial dysfunction. More recently, features of acute-phase activation and low-grade inflammation, including elevated levels of fibrinogen, C-reactive protein and interleukin-6, have been associated with (central) obesity. Adipose tissue generation of cytokines has been shown in vitro and in vivo, and a number of novel cytokine-like molecules, collectively termed adipocytokines, have been identified as adipocyte products. While several of these, such as tumour necrosis factor-alpha, may act predominantly in autocrine or paracrine fashion, others are released into the systemic circulation, acting as signalling molecules to remote tissues, including liver, skeletal muscle and endothelium. A clearer understanding of adipose tissue signalling, and its contribution to the state of low-grade inflammation of obesity, will require physiological, as well as cellular and molecular, studies.
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PMID:Adipose tissue, insulin action and vascular disease: inflammatory signals. 1470 40

Protein-energy malnutrition (PEM) and inflammation are common in patients with chronic kidney disease (CKD) and worsen as the CKD progresses toward the end-stage renal disease (ESRD). These conditions are major predictors of poor clinical outcome in kidney failure, as reflected by a strong association between hypoalbuminemia and cardiovascular disease (CVD). It has been suggested that inflammation is the cause of both PEM and CVD and, hence, the main link among these conditions, but these hypotheses are not well established. Increased release or activation of inflammatory cytokines, such as interleukin-6 or tumor necrosis factor alpha, may suppress appetite, cause muscle proteolysis and hypoalbuminemia, and may be involved in atherogenesis. Increasing serum levels of proinflammatory cytokines caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions may lead to inflammation in CKD patients. In hemodialysis patients, the exposure to dialysis tubing and dialysis membranes, poor quality of dialysis water, back-filtration or back-diffusion of contaminants, and foreign bodies in dialysis access maybe additional causes of inflammation. Similarly, episodes of overt or latent peritonitis, peritoneal dialysis (PD) catheter and its related infections, and constant exposure to PD solution may contribute to inflammation in these patients. The degree to which PEM in dialysis patients is caused by inflammation is not clear. Because both PEM and inflammation are strongly associated with each other and can change many nutritional measures and outcome concurrently in the same direction, the terms malnutrition-inflammation complex syndrome (MICS) and/or malnutrition-inflammation-atherosclerosis (MIA) have been suggested to denote the important contribution of both of these conditions to poor clinical outcome. Maintenance dialysis patients who are underweight or who have low serum levels of cholesterol, creatinine, or homocysteine may be suffering from the MICS/MIA and its subsequent poor outcome. Consequently, obesity and hypercholesterolemia may appear protective, which is known as reverse epidemiology. Although MICS/MIA may have a significant contribution in reversing the traditional CVD risk factors in dialysis patients, it is not clear whether PEM or inflammation and their complications can be effectively managed in CKD and ESRD or whether their management improves clinical outcome.
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PMID:Inflammation and nutrition in renal insufficiency. 1470 70

The fat-derived protein adiponectin is an important insulin-sensitizing adipocytokine which is downregulated in insulin resistance and obesity. Recently, two receptors of this adipose-expressed protein called adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) have been cloned. To clarify expression and regulation of these receptors in fat cells, AdipoR1 and AdipoR2 mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction during differentiation of 3T3-L1 adipocytes and after treatment with various hormones known to induce insulin resistance. Interestingly, AdipoR2 synthesis was significantly increased up to 4.8-fold during differentiation of 3T3-L1 preadipocytes, whereas AdipoR1 expression was only augmented up to 1.4-fold. Furthermore, growth hormone (GH) induced AdipoR2, but not AdipoR1 mRNA by up to 2.4-fold in a dose- and time-dependent fashion with significant stimulation detectable at concentrations as low as 5 ng/ml GH and as early as 2 h after effector addition. The positive effect of GH on AdipoR2 expression could be reversed by withdrawal of the hormone for 24 h. In contrast, other key hormones involved in the regulation of insulin resistance and energy metabolism such as insulin, isoproterenol, dexamethasone, triiodothyronine, angiotensin 2, tumor necrosis factor alpha, and interleukin-6 did not influence AdipoR1 and AdipoR2 synthesis in vitro. Taken together, our results suggest that AdipoR2 expression is differentiation-dependent and selectively regulated by GH implying a potential role of this hormone in adiponectin-associated alterations of insulin sensitivity and energy homeostasis.
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PMID:Growth hormone is a positive regulator of adiponectin receptor 2 in 3T3-L1 adipocytes. 1475 11


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