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)

Liver cirrhosis is characterized by a severe impairment of the growth hormone/insulin-like growth factor-1 (GH-IGF-1) axis, that is, acquired GH resistance. The condition of the GH-IGF-1 axis in the phase of chronic liver disease (CLD) preceding cirrhosis, however, remains uncertain. The origin of GH resistance during CLD is multifactorial, and to date, the liver functional mass is considered to play a major role. Although proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta, were found to be elevated in patients with CLD and were shown to induce a state of GH resistance in other disease models, their involvement in the pathogenesis of GH resistance during CLD has never been investigated. We characterized the GH-IGF-1 axis by analyzing the individual components of the axis (GH, IGF-1, IGF-binding protein-3 [IGFBP-3], acid-labile subunit [ALS]) and the corresponding ratios (GH/IGF-1, GH/IGFBP-3, and GH/ALS) and verified the links with circulating proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), in 34 patients with CLD and 12 healthy controls. Evolution of CLD from chronic hepatitis (CH, n = 17) to cirrhosis (CIR, n = 17) was associated with a progressive increase of GH resistance indices (e.g., GH/IGF-1 ratio: controls 0.5 +/- 0.9, CH 15.9 +/- 31.2, p < 0.01 vs. controls; CIR 188.4 +/- 282.7 mU/nmol, p < 0.001 vs. CH and controls), indicating its onset also in the early stages of CLD. The progressive increase in GH resistance indices matched the increase of circulatory TNF-alpha (e.g., TNF-alpha vs. GH/IGF-1, r = 0.54, p < 0.001). A similar trend was found for IL-6 without reaching statistical significance (r = 0.23, p = 0.13). We found undetectable levels of IL-1beta in our sample of patients and controls. We conclude that proinflammatory cytokines play an important role in the pathogenesis of GH resistance in CLD, but TNF-alpha is a major factor. In addition, GH resistance is present in CLD from the early stages. These results could begin new therapeutic lines of attack in the management of CLD.
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PMID:TNF-alpha and growth hormone resistance in patients with chronic liver disease. 1280 65

Although neither calcium nor vitamin D has been shown to prevent osteoporosis in postmenopausal women alone, the combination does. Both calcium and vitamin D are commonly used in the treatment of osteoporosis. The estrogens and raloxifene both prevent bone loss in postmenopausal women, and the estrogens probably also decrease the risk of first fracture. There is good evidence that raloxifene prevents further fractures in postmenopausal women who have already had fractures and some evidence that estrogen does as well. Calcitonin increases bone mineral density in early postmenopausal women and men with idiopathic osteoporosis, and also reduces the risk of new fractures in osteoporotic women. The bisphosphonate alendronate prevents bone loss and reduces fractures in healthy and osteoporotic postmenopausal women, and in osteoporotic men. Risedronate is more potent and has fewer upper gastrointestinal side effects than alendronate, and reduces the incidence of fractures in osteoporotic women. Intermittent use of the potent bisphosphonate zoledronate also increases bone mineral density and may become an alternative in the prevention and treatment of osteoporosis. All of the agents discussed above prevent bone resorption, whereas teriparatide increases bone formation and is effective in the treatment of osteoporotic women and men. In the treatment of secondary osteoporosis associated with the use of glucocorticoids to treat inflammation or prevent rejection after transplantation, the bisphosphonates are effective. The agents that have undergone some clinical trialing as new or alternative drugs for the treatment of osteoporosis include tibolone, new SERMs, androgens, growth hormone, insulin-like growth factor-1 and stontium ranelate. The targets/drugs that are being developed to inhibit bone resorption include the OPG/ RANKL/RANK system, cathepsin K inhibitors, vitronectin receptor antagonists, estren, the interleukin-6 and gp130 system, cytokines and growth factors. New drugs/targets to promote bone formation include the commonly used lipid-lowering statins and the calcilytic release of PTH.
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PMID:Present and future pharmacotherapy for osteoporosis. 1456 85

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

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

A surface plasmon resonance (SPR) imaging system was constructed and used to detect the affinity-tagged recombinant proteins expressed in Escherichia coli. With regards to model proteins, the hexahistidine-ubiquitin-tagged human growth hormone (His(6)-Ub-hGH), glutathione S-transferase-tagged human interleukin-6 (GST-hIL6), and maltose-binding protein-tagged human interleukin-6 (MBP-hIL6) expressed in E. coli were analyzed. The cell lysates were spotted on gold thin films coated with 11-mercaptoundecanol (MUOH)/dextran derivatized with Ni(II)-iminodiacetic acid (IDA-Ni(II)), glutathione, or cyclodextrin. After a brief washing of the gold chip, SPR imaging measurements were carried out in order to detect the bound affinity-tagged fusion proteins. Using this new approach, rapid high-throughput expression analysis of the affinity-tagged proteins were obtained. The SPR imaging protein chip system used to measure the expression of affinity-tagged proteins in a high-throughput manner is expected to be an attractive alternative to traditional laborious and time-consuming methods, such as SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blots.
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PMID:A fusion protein expression analysis using surface plasmon resonance imaging. 1520 30

Ghrelin, a novel growth hormone-releasing peptide, has been shown to cause a positive energy balance by reducing fat use and stimulating food intake. This study investigated whether plasma ghrelin is associated with clinical parameters in patients with chronic obstructive pulmonary disease. Plasma ghrelin was measured in 50 patients and 13 control subjects, together with anabolic and catabolic factors. Patients were divided into two groups based on body mass index: underweight patients (n = 26) or normal weight patients (n = 24). Plasma ghrelin was significantly higher in underweight patients than in normal weight patients and healthy control subjects. Circulating tumor necrosis factor-alpha, interleukin-6, and norepinephrine were significantly higher in underweight patients than in normal weight patients. Plasma ghrelin correlated negatively with body mass index and correlated positively with catabolic factors such as tumor necrosis factor-alpha and norepinephrine. In addition, plasma ghrelin correlated positively with percent predicted residual volume and residual volume-to-total lung capacity ratio. In conclusion, plasma ghrelin was elevated in underweight patients with chronic obstructive pulmonary disease, and the level was associated with a cachectic state and abnormality of pulmonary function.
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PMID:Elevated plasma ghrelin level in underweight patients with chronic obstructive pulmonary disease. 1527 96

Aging has been associated with a loss of muscle mass that is referred to as 'sarcopenia'. This decrease in muscle tissue begins around the age of 50 years, but becomes more dramatic beyond the 60th year of life. Loss of muscle mass among the aged directly results in diminished muscle function. Decreased strength and power contribute to the high incidence of accidental falls observed among the elderly and can compromise quality of life. Moreover, sarcopenia has been linked to several chronic afflictions that are common among the aged, including osteoporosis, insulin resistance and arthritis. Loss of muscle fibre number is the principal cause of sarcopenia, although fibre atrophy--particularly among type II fibres--is also involved. Several physiological mechanisms have been implicated in the development of sarcopenia. Denervation results in the loss of motor units and thus, muscle fibres. A decrease in the production of anabolic hormones such as testosterone, growth hormone and insulin-like growth factor-1 impairs the capacity of skeletal muscle to incorporate amino acids and synthesise proteins. An increase in the release of catabolic agents, specifically interleukin-6, amplifies the rate of muscle wasting among the elderly. Given the demographic trends evident in most western societies, i.e. increased number of those considered aged, management interventions for sarcopenia must become a major goal of the healthcare profession.
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PMID:Effects of aging on muscle fibre type and size. 1546 13

Leptin is 16 kDa adipokine that links nutritional status with neuroendocrine and immune functions. Initially thought to be a satiety factor that regulates body weight by inhibiting food intake and stimulating energy expenditure, leptin is a pleiotropic hormone whose multiple effects include regulation of endocrine function, reproduction, and immunity. Leptin can be considered as a pro-inflammatory cytokine that belongs to the family of long-chain helical cytokines and has structural similarity with interleukin-6, prolactin, growth hormone, IL-12, IL-15, granulocyte colony-stimulating factor and oncostatin M. Because of its dual nature as a hormone and cytokine, leptin links the neuroendocrine and the immune system. The role of leptin in the modulation of immune response and inflammation has recently become increasingly evident. The increase in leptin production that occurs during infection and inflammation strongly suggests that leptin is a part of the cytokine network which governs the inflammatory-immune response and the host defense mechanisms. Leptin plays an important role in inflammatory processes involving T cells and has been reported to modulate T-helper cells activity in the cellular immune response. Several studies have implicated leptin in the pathogenesis of autoimmune inflammatory conditions, such as experimental autoimmune encephalomyelitis, type 1 diabetes, rheumatoid arthritis, and intestinal inflammation. Very recently, a key role for leptin in osteoarthritis has been demonstrated: leptin indeed exhibits, in concert with other pro-inflammatory cytokines, a detrimental effect on articular cartilage by promoting nitric oxide synthesis in chondrocytes. Here, we review the recent advances regarding leptin biology with a special focus on those actions relevant to the role of leptin in the pathophysiology of inflammatory processes and immune responses.
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PMID:Leptin, from fat to inflammation: old questions and new insights. 1564 35

The purpose of this study was to determine the effect of pre-exercise high carbohydrate meals with high glycemic index (HGI) or low glycemic index (LGI) on blood leukocyte redistribution during subsequent endurance exercise. Eight male subjects performed a 90-min run on a treadmill at 70 % VO2max 3 h after ingesting an isocaloric HGI or LGI meal with GI values of 77 and 37, respectively. Blood counts of leukocytes, and neutrophils and the neutrophil/lymphocyte ratio were significantly lower in LGI than HGI at 90 min of exercise (P < 0.05). The plasma glucose concentrations were significantly higher in LGI than HGI between 15 min and 45 min of exercise. There were, however, no differences in plasma cortisol, growth hormone, and interleukin-6 concentrations between trials. Thus, the GI of a pre-exercise meal influences leukocyte trafficking and plasma glucose but has limited effects on circulating stress hormone and cytokine responses to exercise.
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PMID:The effects of pre-exercise high carbohydrate meals with different glycemic indices on blood leukocyte redistribution, IL-6, and hormonal responses during a subsequent prolonged exercise. 1565 70

The proinflammatory cytokine interleukin-6 (IL-6) may modulate the onset and progression of complications of diabetes. As this cytokine increases after exercise, and many other exercise responses are altered by prior glycemic fluctuations, we hypothesized that prior hyperglycemia might exacerbate the IL-6 response to exercise. Twenty children with type 1 diabetes (12 boys/8 girls, age 12-15 yr) performed 29 exercise studies (30-min intermittent cycling at approximately 80% peak O2 uptake). Children were divided into four groups based on highest morning glycemic reading [blood glucose (BG) < 150, BG 151-200, BG 201-300, or BG > 300 mg/dl]. All exercise studies were performed in the late morning, after hyperglycemia had been corrected and steady-state conditions (plasma glucose < 120 mg/dl, basal insulin infusion) had been maintained for > or = 90 min. Blood samples for IL-6, growth factors, and counterregulatory hormones were drawn at pre-, end-, and 30 min postexercise time points. At all time points, circulating IL-6 was lowest in BG < 150 and progressively higher in the other three groups. The exercise-induced increment also followed a similar dose-response pattern (BG < 150, 0.6 +/- 0.2 ng/ml; BG 151-200, 1.2 +/- 0.8 ng/ml; BG 201-300, 2.1 +/- 1.1 ng/ml; BG > 300, 3.2 +/- 1.4 ng/ml). Other measured variables (growth hormone, IGF-I, glucagon, epinephrine, cortisol) were not influenced by prior hyperglycemia. Recent prior hyperglycemia markedly influenced baseline and exercise-induced levels of IL-6 in a group of peripubertal children with type 1 diabetes. While exercise is widely encouraged and indeed often considered part of diabetic management, our data underscore the necessity to completely understand all adaptive mechanisms associated with physical activity, particularly in the context of the developing diabetic child.
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PMID:Effect of prior hyperglycemia on IL-6 responses to exercise in children with type 1 diabetes. 1633 21


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