Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus, hyperlipidemia, hypertension and atherosclerotic diseases have recently defined as typical life style-related diseases. A common background of these life style-related diseases is overnutrition and its consequence, obesity. Recent advances in the biology of adipose tissue have revealed that adipose is not simply an energy storage organ but it also secretes a variety of molecules which affect the metabolism of the whole body. Through a systematic search of active genes in adipose tissue, we found that adipose tissue, especially visceral fat expressed numerous genes for secretory proteins. Among them, plasminogen activator inhibitor-1(PAI-1) was over expressed in the visceral fat in an animal model of obesity. Plasma level of PAI-1 was closely correlated with visceral adiposity in human. Thus, PAI-1 secreted from visceral fat may play an important role in vascular disease in visceral obesity. Adiponectin, a novel adipose-specific gene product, is abundantly presented in human plasma. This molecule has been shown to have protective roles against atherosclerotic vascular changes and its plasma level is negatively correlated with visceral adiposity. In conclusion, dysregulated secretion of these adipose-specific secretory proteins(adipocytokines) may have important roles in the development of life style-related diseases, especially atherosclerotic diseases.
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PMID:[Life style-related disease]. 1119 54

Adiponectin, also referred to as AdipoQ or ACRP30, is a plasma protein produced and secreted exclusively from adipose tissue. The protein contains a collagen-like domain and a C1q-like globular domain. A protease-generated globular segment enhances fatty acid oxidation in muscles, thereby modulating lipid and glucose metabolism. Plasma adiponectin levels are inversely correlated with the severity of insulin resistance. A recent genome-wide scan study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Here, we screened Japanese patients with type 2 diabetes and age- and BMI-matched nondiabetic control subjects for mutations in adiponectin gene. We identified four missense mutations (R112C, I164T, R221S, and H241P) in the globular domain. Among these mutations, the frequency of I164T mutation was significantly higher in type 2 diabetic patients than in age- and BMI- matched control subjects (P < 0.01). Furthermore, plasma adiponectin concentrations of subjects carrying I164T mutation were lower than those of subjects without the mutation. All the subjects carrying I164T mutation showed some feature of metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and atherosclerosis. Our findings suggest that I164T mutation is associated with low plasma adiponectin concentration and type 2 diabetes.
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PMID:Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. 1208 69

Adiponectin, an adipocyte-derived protein, consists of collagen-like fibrous and complement C1q-like globular domains, and circulates in human plasma in a multimeric form. The protein exhibits anti-diabetic and anti-atherogenic activities. However, adiponectin plasma concentrations are low in obese subjects, and hypoadiponectinemia is associated with the metabolic syndrome, which is a cluster of insulin resistance, type 2 diabetes mellitus, hypertension, and dyslipidemia. We have recently reported a missense mutation in the adiponectin gene, in which isoleucine at position 164 in the globular domain is substituted with threonine (I164T). Subjects with this mutation showed markedly low level of plasma adiponectin and clinical features of the metabolic syndrome. Here, we examined the molecular characteristics of the mutant protein associated with a genetic cause of hypoadiponectinemia. The current study revealed (1) the mutant protein showed an oligomerization state similar to the wild-type as determined by gel filtration chromatography and, (2) the mutant protein exhibited normal insulin-sensitizing activity, but (3) pulse-chase study showed abnormal secretion of the mutant protein from adipose tissues. Our results suggest that I164T mutation is associated with hypoadiponectinemia through disturbed secretion into plasma, which may contribute to the development of the metabolic syndrome.
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PMID:Disturbed secretion of mutant adiponectin associated with the metabolic syndrome. 1278 2

Adiponectin, an adipocyte-derived protein, has been suggested to play an important role in insulin sensitivity. We examined the association between insulin sensitivity (M value) evaluated by the euglycemic-hyperinsulinemic glucose clamp and adiponectin concentrations in 30 essential hypertensives (EHT) and 20 normotensives (NT) and investigated the effect of blockade of the renin-angiotensin system (RAS) on adiponectin concentrations. EHT were divided into 12 insulin-resistant EHT (EHT-R) and 18 non-insulin-resistant EHT (EHT-N) using mean-1 SD of the M value in NT. There were no intergroup differences in age, gender, and body mass index (BMI). EHT-R had significantly higher levels of insulin and triglyceride and lower levels of adiponectin than did NT and EHT-N. EHT-R had higher levels of free fatty acid and lower levels of high-density lipoprotein (HDL) cholesterol than did EHT-N. Adiponectin concentrations were positively correlated with M value and HDL cholesterol and negatively correlated with BMI, insulin, free fatty acid, and triglyceride but not with blood pressure. M value, BMI, and HDL cholesterol were independent determinants of adiponectin concentrations in multiple and stepwise regression analyses. Sixteen EHT were treated with an angiotensin-converting enzyme inhibitor (temocapril, 4 mg/d; n=9) or an angiotensin II receptor blocker (candesartan, 8 mg/d; n=7) for 2 weeks. Treatment with temocapril or candesartan significantly decreased blood pressure and increased M value and adiponectin concentrations but did not affect BMI and HDL cholesterol. These results suggest that hypoadiponectinemia is related to insulin resistance in essential hypertension and that RAS blockade increases adiponectin concentrations with improvement in insulin sensitivity.
Hypertension 2003 Jul
PMID:Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension. 1279 80

Endothelial dysfunction is a crucial feature in the evolution of atherosclerosis. Adiponectin is an adipocyte-specific plasma protein with antiatherogenic and antidiabetic properties. In the present study, we investigated the relation between adiponectin and endothelium-dependent vasodilation. We analyzed endothelial function in 202 hypertensive patients, including those who were not taking any medication. Forearm blood flow was measured by strain-gauge plethysmography. Plasma adiponectin level was highly correlated with the vasodilator response to reactive hyperemia in the total (r=0.257, P<0.001) and no-medication (r=0.296, P=0.026) groups but not with nitroglycerin-induced hyperemia, indicating that adiponectin affected endothelium-dependent vasodilation. Multiple regression analysis of data from all hypertensive patients revealed that plasma adiponectin level was independently correlated with the vasodilator response to reactive hyperemia. Vascular reactivity was also analyzed in aortic rings from adiponectin-knockout (KO) and wild-type (WT) mice. Adiponectin-KO mice showed obesity, hyperglycemia, and hypertension compared with WT mice after 4 weeks on an atherogenic diet. Endothelium-dependent vasodilation in response to acetylcholine was significantly reduced in adiponectin-KO mice compared with WT mice, although no significant difference was observed in endothelium-independent vasodilation in response to sodium nitroprusside. Our observations suggest that hypoadiponectinemia is associated with impaired endothelium-dependent vasorelaxation and that the measurement of plasma adiponectin level might be helpful as a marker of endothelial dysfunction.
Hypertension 2003 Sep
PMID:Association of hypoadiponectinemia with impaired vasoreactivity. 1286 Aug 35

Adiponectin is a recently identified, insulin-sensitizing and anti-inflammatory protein released by adipocytes, which is paradoxically reduced in obesity. It suppresses endothelial activation. Physiological insulin resistance occurs in normal pregnancy and is exaggerated in women with preeclampsia (PE), together with enhanced inflammatory and endothelial activation. Women with increased body mass index (BMI) and insulin resistance are predisposed to PE. We hypothesized that adiponectin concentrations are reduced in normal pregnancy compared with postpartum values and further reduced in women with PE. Fifteen women with PE and 30 control subjects with similar first trimester BMI had adiponectin concentrations measured in the third trimester; postpartum measurements were repeated in 16 control subjects. Adiponectin concentration in healthy pregnant women correlated inversely with early pregnancy BMI (r=-0.47, P=0.01) and fasting insulin concentrations (r=-0.58, P=0.001). However, adiponectin concentrations did not differ significantly in pregnancy and postpartum samples (mean change, -0.15 microg/mL; 95% CI, -2.28 to 1.98, P=0.88). Plasma adiponectin concentrations were markedly elevated (P=0.01) in women with PE (mean, 21.6; SD, 8.18 microg/mL) compared with control subjects (mean, 14.7; SD, 7.06 microg/mL). Moreover, in PE, adiponectin concentrations did not correlate with first trimester BMI or insulin or with serum urate or creatinine concentrations or urinary protein levels. We conclude that plasma adiponectin concentrations are not elevated in normal human pregnancy and paradoxically elevated (by 47%) in women with PE. This may be secondary to exaggerated nonspecific adipocyte lipolysis or as a physiological response to enhance fat utilization and attenuate endothelial damage. Future studies should determine whether adiponectin concentrations help improve prediction of PE.
Hypertension 2003 Nov
PMID:Paradoxical elevation in adiponectin concentrations in women with preeclampsia. 1475 83

Adiponectin is a recently discovered hormone secreted by adipocytes that has been reported to enhance insulin sensitivity. Although insulin resistance and/or compensatory hyperinsulinemia are considered to be involved with hypertension in obese humans, the relationship between plasma adiponectin level and obesity-related hypertension has not been fully clarified. In this study, we investigated the effect of dietary conjugated linoleic acid (CLA), reported as an insulin sensitizer, on plasma adiponectin, plasma insulin, and blood pressure in Zucker diabetic fatty (ZDF) rats. During the onset of obesity, blood pressure increased in ZDF rats. The increase, however, was prevented by dietary CLA. After 8 weeks, accumulated plasma insulin and glucose were also attenuated by CLA feeding. Dietary CLA increased plasma adiponectin levels in ZDF rats and the increase was attributed to the enhanced mRNA expression in white adipose tissue. This study provides the first evidence that dietary CLA increases plasma adiponectin level through the enhancement of mRNA expression. We speculate that the increase alleviates hyperinsulinemia and prevents the onset of hypertension in CLA-fed ZDF rats.
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PMID:Conjugated linoleic acid enhances plasma adiponectin level and alleviates hyperinsulinemia and hypertension in Zucker diabetic fatty (fa/fa) rats. 1452 47

Adiponectin is one of the key molecules in the metabolic syndrome, and its concentration is decreased in obesity, type-2 diabetes, and coronary artery disease. Genetic investigation has revealed that 2 polymorphisms (I164T and G276T) are related to adiponectin concentration and diabetes. To examine whether adiponectin affects hypertension genetically or biologically, we performed a case-control study. A total of 446 diagnosed cases of hypertension (HT) in men and 312 normotensive (NT) men were enrolled in this study. Plasma adiponectin concentration was measured using an enzyme-linked immunosorbent assay system. Single nucleotide polymorphisms were determined by TaqMan polymerase chain reaction method. After adjustment for confounding factors, adiponectin concentration was significantly lower in HT (HT: 5.2+/-0.2 microg/mL; NT: 6.1+/-0.2 microg/mL; P<0.001). Furthermore, multiple regression analysis indicated that hypoadiponectinemia was an independent risk factor for hypertension (P<0.001). Blood pressure was inversely associated with adiponectin concentration in normotensives regardless of insulin resistance. In subjects carrying the TC genotype of the I164T polymorphism, adiponectin concentration was significantly lower (TC: 2.6+/-0.9 microg/mL; TT: 5.5+/-0.1 microg/mL; P<0.01), and most of them had hypertension. In contrast, the G276T polymorphism was not associated with adiponectin concentration or hypertension. In conclusion, hypoadiponectinemia is a marker for predisposition to hypertension in men.
Hypertension 2004 Jun
PMID:Hypoadiponectinemia is an independent risk factor for hypertension. 1512 70

Cardiovascular disease accounts for an overwhelming proportion of the morbidity and mortality suffered by patients with obesity and type 2 diabetes mellitus, and recent work has elucidated several potential mechanisms by which increased adiposity enhances cardiovascular risk. Excess adipose tissue, especially in certain compartments, leads to reduced insulin sensitivity in metabolically responsive tissues, which is frequently associated with a set of cardiovascular risk factors, including hyperinsulinemia, hypertension, dyslipidemia, and glucose intolerance. Increasing attention has also been paid to the direct vascular effects of plasma proteins that originate from adipose tissue, especially adiponectin, which exhibits potent antiinflammatory and antiatherosclerotic effects. This brief review will summarize recent work on the vascular actions of adiponectin, which complements the growing body of information on its insulin-sensitizing effects in glucose and lipid metabolism. Adiponectin is now a recognized component of a novel signaling network among adipocytes, insulin-sensitive tissues, and vascular function that has important consequences for cardiovascular risk.
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PMID:Adiponectin: A novel adipokine linking adipocytes and vascular function. 1518 Oct 24

Here we investigated the biological functions of adiponectin, a fat-derived hormone, by disrupting the gene encodes it in mice. Adiponectin knockout mice (KO) exhibited severe diet-induced insulin resistance with reduced IRS-1-associated P13-kinase activity in muscle. KO also revealed severe neo-intimal thickening in response to vascular-injury and hypertension induced by salt diet. Carbon-tetrachloride induced severe liver fibrosis in KO with the elevated gene expression of growth factors. These phenotypes in KO were reversed by viral-mediated production of adiponectin. Our results indicate that adiponectin should be one of key molecule of the metabolic syndrome and may be a new therapeutic target for the metabolic syndrome.
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PMID:[Adiponectin knockout mice]. 1520 43


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