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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic syndrome incorporates into a single entity, insulin resistance and its associated cluster of related cardiovascular metabolic risk factors including type 2 diabetes mellitus, essential hypertension, dyslipidamia and central obesity. Various hypotheses (thrifty genotype/phenotype, limbic-hypothalamic and altered homeostatic mechanisms) have been used to explain the interaction between genetic, intrauterine and environmental factors, leading to this enigmatic concept. Current interest addresses the roles of fat-derived adiponectin, inflammatory markers (C-reactive protein, leucocytes, interleukin and tumour necrosis factor), endothelial dysfunction and disordered haemostasis (plasminogen activator inhibitor-1 and fibrinogen). Angiotensin II, endothelin-1 and increased salt sensitivity contribute to the development of hypertension in metabolic syndrome. The main significance of the syndrome is the heightened risk of cardiovascular morbidity and mortality arising from increased atherogenic potential. Therapeutic interventions are multidimensional in approach, and aimed at enhancing insulin sensitivity and ameliorating the consequences of insulin resistance. Promotion of African native lifestyle characterised by high degree of physical activity and fibre diet is and appropriate tool for primary prevention of metabolic syndrome.
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PMID:The metabolic syndrome: Review of current concepts. 1727 22

Experimental and clinical evidence is now available that antagonism of angiotensin II (Ang II) with both angiotensin-converting enzyme inhibitors and Ang II receptor antagonists (AIIAs) is effective in slowing the rate of renal functional loss in patients affected by proteinuric kidney diseases. Among AIIAs, telmisartan has been shown to be characterised by a potent and long lasting antihypertensive effect that may be associated with another specific effect of this molecule, the partial agonism of the peroxisome-activated receptor-gamma. Although this action has also been observed with other AIIAs, telmisartan seems to exert a more effective and specific action as in such a way to influence beneficially adipocyte metabolism, diabetes onset and insulin resistance. Recently, we have demonstrated, at the experimental and clinical level, that sustained blockade of Ang II biological activity with this class of compounds can potentially reduce the progression of renal dysfunction and in some circumstances induce the regression of renal functional and structural changes. In this review we analyse available experimental and clinical data that suggest that blocking Ang II with telmisartan may effectively ameliorate renal dysfunction in patients affected by the now frequently observed condition termed metabolic syndrome.
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PMID:Potential protective effects of telmisartan on renal function deterioration. 1731 86

Angiotensin II (Ang II) is able to induce free radical generation in neutrophils, which is more elevated in neutrophils of patients with hypercholesterolemia (HC). In addition, the signal processing through angiotensin I (Ang I) receptors is altered. In present study, we compared the Ang II-triggered free radical generation of neutrophils obtained from patients with relatively isolated forms of metabolic syndrome (MS) with membrane-bound cholesterol content and membrane fluidity. We determined the enhancement of Ang II-induced superoxide anion and leukotriene C(4) (LTC(4)) generation, membrane fluidity and cell-bound cholesterol content of neutrophils obtained from 12 control subjects, 11 patients with obesity (Ob), 10 patients with type 2 diabetes mellitus (t2-DM) and 12 patients with HC. The alteration of signal processing was studied after preincubation with different inhibiting drugs. Superoxide anion, LTC(4) production and membrane rigidity were increased in the following order: control < Ob < t2-DM < HC. Both Ang II-induced superoxide anion and LTC(4) generation were decreased in control cells by pertussis toxin and fluvastatin (Flu), whereas in each patient group, mepacrin, verapamil and Flu were effective, suggesting alterations in signal pathways, which may be attributed to isoprenylation. The enhancement of superoxide anion and LTC(4) generation correlated significantly with membrane rigidity, independently from the experimental groups and membrane-bound cholesterol content. Membrane rigidity of neutrophils, obtained from patients with MS, plays a role in Ang II-induced free radical generation independent of intracellular cholesterol homeostasis.
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PMID:The association between angiotensin II-induced free radical generation and membrane fluidity in neutrophils of patients with metabolic syndrome. 1754 12

Angiotensin II Receptor blockers (ARBs) are an important addition to the current range of medications available for treating a wide spectrum of diseases including cardiovascular diseases. Coronary heart disease (CHD) is the most common cause of death in the United Kingdom and worldwide. More importantly, the presence of the metabolic syndrome and the likelihood of diabetes mellitus taking on epidemic proportions in the years to come all threaten to maintain the mortality rate due to CHD. This review article focuses on the clinical studies that have helped define the trends in the usage of these agents in the prevention and treatment of diabetes mellitus and its complications and also explores possible mechanisms of action and future developments.
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PMID:The role of angiotensin II type 1 receptor blockers in the prevention and management of diabetes mellitus. 1769 55

An overactive renin-angiotensin system is associated with obesity and the metabolic syndrome. However, the mechanisms behind it are unclear. Cleaving angiotensinogen to angiotensin I by renin is a rate-limiting step of angiotensin II production, but renin is suggested to have angiotensin-independent effects. We generated mice lacking renin (Ren1c) using embryonic stem cells from C57BL/6 mice, a strain prone to diet-induced obesity. Ren1c(-/-) mice are lean, insulin sensitive, and resistant to diet-induced obesity without changes in food intake and physical activity. The lean phenotype is likely due to a higher metabolic rate and gastrointestinal loss of dietary fat. Most of the metabolic changes in Ren1c(-/-) mice were reversed by angiotensin II administration. These results support a role for angiotensin II in the pathogenesis of diet-induced obesity and insulin resistance.
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PMID:Increased energy expenditure, dietary fat wasting, and resistance to diet-induced obesity in mice lacking renin. 1805 19

1 A fructose-enriched diet induces hypertension, metabolic alterations and insulin resistance in rats, resembling human metabolic syndrome. Previously, we found that prostanoid production was altered in fructose-fed rats. 2 This study analysed the effects of incubation with noradrenaline (NA) and angiotensin II (Ang II) on prostanoid release in mesenteric vascular beds from control and fructose-fed rats. Animals which received fructose solution (10% w/v) for 22 weeks showed higher systolic blood pressure and triglyceridaemia. 3 In controls, NA increased 6-keto-prostaglandin (PG) F(1)alpha (prostacyclin metabolite) and thromboxane (TX) production. Ang II increased only TX release. In fructose-fed animals, NA increased 6-keto-PG F(1)alpha and TX. PGF(2)alpha (vasoconstrictor) was also elevated. Ang II also increased PGF(2)alpha and PGE(2) levels. 4 In conclusion, in fructose rats Ang II in vitro stimulates a vasoconstrictor prostanoid not stimulated in controls. This could be related to the observed in vivo blood pressure increase. In fructose-fed animals, NA and Ang II also augment vasodilator prostanoids, suggesting a compensatory mechanism because of long-term hypertension.
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PMID:Noradrenaline and angiotensin II modify vascular prostanoid release in fructose-fed hypertensive rats. 1807 76

The metabolic syndrome is a risk factor for the development of chronic kidney disease. Angiotensin II type 1 receptor blockers (ARBs) and thiazolidinediones (TZDs) provide renovascular protection, probably in the metabolic syndrome. However, the effect of both agents administered together in patients with metabolic syndrome remains to be determined. The aim of this study was to assess the effects of ARB plus TZD combination therapy in Zucker obese rats fed a high-protein diet, an animal model of metabolic syndrome and renal injury. Zucker obese rats were fed a high-protein diet (OHP; n=6), a high-protein diet containing candesartan, an ARB (OHP+C; n=6), or a high-protein diet containing both candesartan and pioglitazone (OHP+CP; n=6) for 12 weeks. Systolic blood pressure and urinary protein excretion were measured throughout the study, and renal histology and immunohistochemistry were assessed at 12 weeks. OHP rats developed hypertension (157+/-4 mmHg) and proteinuria (178+/-44 mg/d), and these conditions were significantly ameliorated by candesartan (to 143+/-3 mmHg and 84+/-25 mg/d, respectively). Pioglitazone enhanced the antihypertensive and anti-proteinuric effects of candesartan (121+/-3 mmHg, 16+/-8 mg/d, respectively). Histologically, candesartan ameliorated glomerulosclerosis, podocyte injury, interstitial fibrosis and monocyte/macrophage infiltration into the tubulointerstitium in the kidneys of OHP rats. Pioglitazone abrogated residual interstitial fibrosis in the kidneys of OHP+C rats. Our results suggested that pioglitazone augmented the antihypertensive, anti-proteinuric and possibly renal anti-fibrotic actions of candesartan in Zucker obese rats fed a high-protein diet. The combination therapy of ARB and TZD may protect against renal injury in patients with metabolic syndrome.
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PMID:Pioglitazone enhances the antihypertensive and renoprotective effects of candesartan in Zucker obese rats fed a high-protein diet. 1863 87

Essential hypertension is an insulin resistant state. Early insulin signaling steps are impaired in essential hypertension and a large body of data suggests that there is a crosstalk at multiple levels between the signal transduction pathways that mediate insulin and angiotensin II actions. At the extracellular level the angiotensin converting enzyme (ACE) regulates the synthesis of angiotensin II and bradykinin that is a powerful vasodilator. At early intracellular level angiotensin II acts on JAK-2/IRS1-IRS2/PI3-kinase, JNK and ERK to phosphorylate serine residues of key elements of insulin signaling pathway therefore inhibiting signaling by the insulin receptor. On another level angiotensin II inhibits the insulin signaling inducing the regulatory protein SOCS 3. Angiotensin II acting through the AT1 receptor can inhibit insulin-induced nitric oxide (NO) production by activating ERK 1/2 and JNK and enhances the activity of NADPH oxidase that leads to an increased reactive oxygen species generation. From the clinical standpoint, the inhibition of the renin angiotensin system improves insulin sensitivity and decreases the incidence of Type 2 Diabetes Mellitus (T2DM). This might represent an alternative approach to prevent type 2 diabetes in patients with hypertension and metabolic syndrome, (i.e. insulin resistant patients). This review will discuss: a) the molecular mechanisms of the crosstalk between the insulin and angiotensin II signaling systems b) the results of clinical studies employing drugs targeting the renin-angiotensin II-aldosterone systems and their role in glucose metabolism and diabetes prevention.
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PMID:The crosstalk between insulin and renin-angiotensin-aldosterone signaling systems and its effect on glucose metabolism and diabetes prevention. 1885 18

The role of the Renin-Angiotensin-Aldosterone system (RAAS) on the development of insulin resistance and cardiovascular disease is an area of growing interest. Most of the deleterious actions of the RAAS on insulin sensitivity appear to be mediated through activation of the Angiotensin II (Ang II) Receptor type 1 (AT(1)R) and increased production of mineralocorticoids. The underlying mechanisms leading to impaired insulin sensitivity remain to be fully elucidated, but involve increased production of reactive oxygen species and oxidative stress. Both experimental and clinical studies also implicate aldosterone in the development of insulin resistance, hypertension, endothelial dysfunction, cardiovascular tissue fibrosis, remodelling, inflammation and oxidative stress. There is abundant evidence linking aldosterone, through non-genomic actions, to defective intracellular insulin signalling, impaired glucose homeostasis and systemic insulin resistance not only in skeletal muscle and liver but also in cardiovascular tissue. Blockade of the different components of the RAAS, in particular Ang II and AT(1)R, results in attenuation of insulin resistance, glucose homeostasis, as well as decreased cardiovascular disease morbidity and mortality. These beneficial effects go beyond to those expected with isolated control of hypertension. This review focuses on the role of Ang II and aldosterone in the pathogenesis of insulin resistance, as well as in clinical relevance of RAAS blockade in the prevention and treatment of the metabolic syndrome and cardiovascular disease.
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PMID:Role of aldosterone and angiotensin II in insulin resistance: an update. 1913 13

Renin angiotensin aldosterone system (RAAS) in the central nervous system (CNS) and therapeutical effects of angiotensin II receptor blockers (ARBs) have been highlighted. In stroke, clinical trials exhibit to prevent primary onset or recurrence of stroke beyond anti-hypertensive effect, inhibition of atrial fibrillation and diabetes mellitus. ARB could be also expected to prevent cognitive impairment induced by such as Alzheimer disease, stroke and metabolic syndrome; however, clinical evidence has not been revealed to date. Angiotensin II levels in cerebrospinal fluid in patients with neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis is reduced, suggesting the role of RAAS in neural intractable diseases. These findings will provide us new therapeutic approaches of ARB in CNS disorder in t hefuture.
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PMID:[New insights of ARB in central nervous system]. 1934 36


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