Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors investigated in 18 patients with essential hypertension the action of celiprolol (usually in combination with a diuretic) on the glucose and lipid metabolism in an open three-month trial. They evaluated the glucose, insulin and C-peptide concentration during an oral glucose tolerance test (oGTT) and the serum lipid concentration before and after treatment. It was revealed: 1. There are no significant changes in the glucose, insulin and C-peptide concentrations on fasting, 2. There is a significant reduction of the blood sugar level during the second hour of oGTT after treatment, 3. A significant reduction of glucose and C-peptide during the 1st and 2nd hour of oGTT after treatment in the sub-group with a poor glucose tolerance/insulin sensitivity, 4. There are no differences between the mentioned variables in hypertonic patients with a normal glucose metabolism, 5. There are no significant changes in values of total cholesterol, HDL-, LDL and VLDL-cholesterol and triacylglycerols. Celiprolol can exert in combination with diuretics also a favourable effect on the glucose tolerance/insulin sensitivity in patients with essential hypertension and metabolic syndrome.
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PMID:[Celiprolol improves glucose metabolism in essential hypertension]. 982 78

Experimental models of genetic hypertension are used to develop paradigms to study human essential hypertension while removing some of the complexity inherent in the study of human subjects. Since 1991 several quantitative trait loci responsible for blood pressure regulation have been identified in various rat crosses. More recently, a series of interesting quantitative trait loci influencing cardiac hypertrophy, stroke, metabolic syndrome and renal damage has also been described. It is recognized that the identification of large chromosomal regions containing a quantitative trait locus is only a first step towards gene identification. The next step is the production of congenic strains and substrains to confirm the existence of the quantitative trait locus and to narrow down the chromosomal region of interest. Several congenic strains have already been produced, with further refinement of the methodology currently in progress. The ultimate goal is to achieve positional cloning of the causal gene, a task which has so far been elusive. There are several areas of cross-fertilization between experimental and human genetics of hypertension, with a successful transfer of two loci directly from rats to humans and with new pharmacogenetic approaches which may be utilized in both experimental and clinical settings.
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PMID:Genetics of experimental hypertension. 988 70

Insulin resistance is one of the cardinal pathophysiological components of the metabolic syndrome, type 2 diabetes, and frequently co-exists with essential hypertension. Although insulin resistance is defined as inadequate target organ (muscle, liver and fat) responsiveness and/or sensitivity to insulin, the primary defect may be located in the target organs themselves or at their remote controller--the central nervous system. One of the ways of resolving this dilemma is studying the mechanisms of action of drugs that have insulin-sensitizing properties. In this brief review we discuss how the known and potential insulin sensitizers: metformin, appetite suppressants, thiazolidinediones, and the new class of centrally acting antihypertensive drugs, I1-receptor agonists, may work.
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PMID:Insulin resistance: site of the primary defect or how the current and the emerging therapies work. 1021 39

Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR. BN-Il6/Npy strain.
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PMID:Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension. 1037 71

Suggestive evidence has been obtained in a "4-corners" study for involvement of the glucocorticoid receptor gene (GRL) in genetic variation in blood pressure. Therefore, we tested markers at the GRL locus for association and linkage with essential hypertension (HT). For the association study, we used a well-characterized group of 129 white Australians of Anglo-Celtic extraction who had HT, a strong family history of HT (2 parents with the disease), and early-onset moderate-to-severe disease. Controls were 195 normotensive white subjects whose parents were normotensive past the age of 50 years. For the linkage study, we used 175 sibling pairs of similar ancestry. The case-control groups were genotyped for an Asn363Ser variant in exon 2, a G/T variant in intron 4, and a microsatellite marker (D5S207) tightly linked (<200 kb) to GRL. For the groups as a whole, no association or linkage was observed after analysis of data by a variety of statistical tests. Analysis of sibling-pair data gave an exclusion score of -3.8 for the logarithm of the odds for linkage, indicating significant nonlinkage. However, in females, weak association of the intron 4 polymorphism with HT (P=0.03), as well as with systolic and diastolic blood pressure in all subjects (P=0. 04 and 0.03), was observed, and in the case of the D5S207 marker, association with HT was apparent in males (P=0.0001). Thus, although our results provide no overall support for GRL in HT etiology, apparent gender-specific associations could exist in this genomic region, possibly reflecting correlated occurrence with (an)other metabolic syndrome disorder(s).
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PMID:Association and linkage analyses of glucocorticoid receptor gene markers in essential hypertension. 1060 Nov 16

To evaluate whether increased levels of reactive oxygen species (ROS) are involved in the pathogenesis of essential hypertension (EH) and non-insulin-dependent diabetes mellitus (NIDDM), both resting and stimulated levels of intracellular ROS were measured in lymphocytes from patients with EH (n = 10), NIDDM (n = 16) and age-matched healthy individuals (control subjects, n = 19). ROS was monitored with the dye, dihydrorhodamine-123 (DHR; 1 micromol/L) in the presence or absence of superoxide dismutase (superoxide scavenger), sodium azide (singlet oxygen/hydrogen peroxide scavenger), genistein (tyrosine kinase inhibitor), or bisindolylmaleimide (protein kinase C inhibitor). Simultaneous monitoring of cytosolic [Ca2+]i was done with fura-2. Resting ROS levels were significantly higher in NIDDM (4.71+/-0.25 nmol/10(6) cells; mean +/- SEM, P<.05) compared with EH (4.03+/-0.22 nmol/10(6) cells) or controls (4.05+/-0.15 nmol/10(6) cells). The formyl-Met-Leu-Phenylalanine-(fMLP)-induced ROS generation was significantly higher in NIDDM (21.92+/-2.23 nmol/10(6) cells; P<.05) compared with EH (14.58+/-1.90 nmol/10(6) cells) or control (16.06+/-1.22 nmol/10(6) cells). The fMLP-induced ROS increase was significantly reduced in the presence of sodium azide in all groups (P<.01) but was largely unaffected in the presence of SOD. Genistein and bisindolylmaleimide significantly inhibited the fMLP-induced ROS in all groups. The fMLP-induced [Ca2+]i increase was significantly higher in NIDDM (71+/-12 nmol/L, P <.01) compared with EH (42+/-4 nmol/L) and control subjects (35+/-3 nmol/L). Phytohemagglutinin was more effective in increasing [Ca2+]i than ROS. It is concluded that ROS may play a role in the metabolic syndrome of NIDDM but not in EH.
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PMID:Reactive oxygen species in essential hypertension and non-insulin-dependent diabetes mellitus. 1061 78

In primary hypertension a mild hyperresponsiveness of hypothalamic, sympatho-hormonal centres to psychosocial stimuli forms a major pathogenetic element, although high salt intake in some subjects may contribute via volume expansion. Hypertension is often associated with another "civilisation" disorder, the metabolic syndrome, defined as abdominal obesity, insulin resistance and dyslipidaemia. According to recent research, the metabolic syndrome has in all likelihood a central neuroendocrine origin in the form of enhanced engagement of the hypothalamic-pituitary-adrenal (HPA) axis. Here the peripheral endocrine perturbations act as triggers for both central obesity and the metabolic abnormalities. The reaction pattern characterising early primary hypertension is identical with, or closely related to, the "defence reaction", while that leading to the metabolic syndrome is similar to that of the "defeat reaction". Both belong to the primitive survival reactions, common to all mammals, though man can control, or at least mask, his outward-behavioural part but not the neuro-hormonal expressions. Animal experiments show how frequent or chronic mental challenges are capable of engaging these limbic-hypothalamic centres, affecting blood pressure regulation as well as endocrine-metabolic regulation. Furthermore, these centres are tightly coupled functionally, and their signals to the periphery often combined. On a long-term basis their engagements appear to be decisive for the development of both primary hypertension and the metabolic syndrome, as suggested by intervention studies. In both these "disorders of civilisation", observations strongly indicate that psychosocial stress, socioeconomic handicaps, lack of exercise, abuse and also psychiatric traits are involved. Such factors, characteristic of current competitive society, probably cause mixed engagements of the two above-mentioned neuro-hormonal patterns, and thereby, with time, primary hypertension and the metabolic syndrome, with end-points such as coronary artery disease, diabetes mellitus type2 and stroke. Susceptibility to such developments is probably enhanced by genetic factors. This overview of recent developments therefore serves to emphasise how both primary hypertension and the metabolic syndrome seem to have a common central origin. Central regulatory factors are often overlooked, partly because it is not realised that limbic-hypothalamic centres are the major regulators of both circulatory and metabolic events, and partly because of the long period of time required before these disease end-points are reached.
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PMID:Hypertension and the metabolic syndrome: closely related central origin? 1085 28

Metabolic syndrome X is a multifaceted syndrome, which occurs frequently in the general population. It is more common in men than in women. A large segment of the adult population of industrialized countries develops the metabolic syndrome, produced by genetic, hormonal and lifestyle factors such as obesity, physical inactivity and certain nutrient excesses. This disease is characterized by the clustering of insulin resistance and hyperinsulinemia, and is often associated with dyslipidemia (atherogenic plasma lipid profile), essential hypertension, abdominal (visceral) obesity, glucose intolerance or noninsulin-dependent diabetes mellitus and an increased risk of cardiovascular events. Abnormalities of blood coagulation (higher plasminogen activator inhibitor type 1 and fibrinogen levels), hyperuricemia and microalbuminuria have also been found in metabolic syndrome X. This review summarizes the present knowledge of abnormalities in this syndrome. Each risk factor is reviewed, and potential criteria for diagnosis and therapeutic targets are discussed. Because patients with metabolic syndrome X accumulate cardiac risk factors, they should be given special attention in terms of diagnosis and treatment.
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PMID:Metabolic syndrome X: a review. 1086 69

Essential hypertension conveys an increased risk of cardiovascular morbidity and mortality. The common finding of an autonomic imbalance in these patients contributes not only to the etiology of hypertension itself, but also to the cardiac risk and resulting adverse sequelae. A high sympathetic tone in particular is responsible for many of the metabolic, hemodynamic, trophic, and rheologic abnormalities that cluster in patients with high blood pressure. Methods to clarify the respective importance of prereceptor versus receptor abnormalities for the etiology of insulin resistance are warranted. Results of large hypertension clinical trials examining the degree of cardioprotection offered by newer medications that are neutral or beneficial to the vast array of underlying abnormalities are a few years away. In the meantime, utilization of antihypertensive drugs that reduce sympathetic overactivity and are metabolically beneficial is a reasonable clinical alternative in hypertensive patients with the metabolic syndrome or with signs of autonomic imbalance.
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PMID:Autonomic imbalance, hypertension, and cardiovascular risk. 1092 30

The metabolic syndrome is a complex association of several risk factors including insulin resistance, dyslipidemia, and essential hypertension. Insulin resistance has been associated with sympathetic activation and endothelial dysfunction, which are the main mechanisms involved in the pathophysiology of hypertension and its related cardiovascular risk. According to the Sixth Report of the Joint National Committee, and guidelines of the World Health Organization/International Society of Hypertension, the presence of multiple risk markers suggests that both hypertension and risk factors should be aggressively managed in order to obtain a better outcome. Primary prevention of obesity at different levels--individual, familial, and social-- starting early in childhood has proven to be cost effective, and will be mandatory to reduce the world epidemic of obesity and its severe consequences.
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PMID:The metabolic syndrome and related cardiovascular risk. 1127 89


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