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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adiponectin, a novel hormone made by fat tissue, regulates energy metabolism and endothelial activation. Serum levels of adiponectin are reduced in conditions that are associated with an increased risk of cardiovascular disease, such as diabetes and the metabolic syndrome. Adiponectin trimers assemble into higher-order oligomers, which have different signaling properties. Adiponectin trimers and a C-terminal globular domain activate AMP-activated protein kinase, whereas hexamer and high-molecular weight isoforms activate nuclear factor-kappa B signaling pathways. Exogenous adiponectin corrects metabolic defects that are associated with insulin resistance, and might protect the endothelium from the progression of cardiovascular disease. Receptors for adiponectin have been described and might provide future therapeutic targets for the treatment of cardiovascular disease.
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PMID:The role of the adipocyte hormone adiponectin in cardiovascular disease. 1578 Aug 20

The aim of the study was to assess the relation of adiponectin levels with the metabolic syndrome in Asian Indians, a high-risk group for diabetes and premature coronary artery disease. The study was conducted on 100 (50 men and 50 women) type 2 diabetic subjects and 100 age and sex matched subjects with normal glucose tolerance selected from the Chennai Urban Rural Epidemiology Study, an ongoing population study in Chennai in southern India. Metabolic syndrome was defined using modified Adult Treatment Panel III (ATPIII) guidelines. Adiponectin values were significantly lower in diabetic subjects (men: 5.2 vs 8.3 microg/mL, P=.00l; women: 7.6 vs 11.1 microg/mL, P<.00l) and those with the metabolic syndrome (men: 5.0 vs 6.8 microg/mL, P=.01; women: 6.5 vs 9.9 microg/mL, P=.001) compared with those without. Linear regression analysis revealed adiponectin to be associated with body mass index (P<.05), waist circumference (P<.01), fasting plasma glucose (P=.001), glycated hemoglobin (P<.001), triglycerides (P<.00l), high-density lipoprotein (HDL) cholesterol (P<.001), cholesterol/HDL ratio (P<.00l), and insulin resistance measured by homeostasis assessment model (P<.00l). Factor analysis identified 2 factors: factor 1, negatively loaded with adiponectin and HDL cholesterol and positively loaded with triglycerides, waist circumference, and insulin resistance measured by homeostasis assessment model; and factor 2, with a positive loading of waist circumference and systolic and diastolic blood pressure. Logistic regression analysis revealed adiponectin to be negatively associated with metabolic syndrome (odds ratio [OR], 0.365; P<.001) even after adjusting for age (OR, 0.344; P<.00l), sex (OR, 0.293; P<.001), and body mass index (OR, 0.292; P<.00l). Lower adiponectin levels are associated with the metabolic syndrome per se and several of its components, particularly, diabetes, insulin resistance, and dyslipidemia in this urban south Indian population.
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PMID:Association of low adiponectin levels with the metabolic syndrome--the Chennai Urban Rural Epidemiology Study (CURES-4). 1579 54

Adiponectin is an adipocyte-derived anti-atherogenic protein. Adiponectin levels are decreased in patients and animal models with obesity, diabetes, and coronary artery disease. However, the mechanism by which adiponectin levels are reduced remains unknown. Since hypoadiponectinemia is closely linked to endothelial dysfunction, we examined the regulation of adiponectin in a rat model of chronic blockade of nitric oxide (NO) synthesis by N omega-nitro-L-arginine methyl ester (L-NAME). Decreased production of NO and increased production of O2- were observed in aorta from L-NAME-treated rats. Plasma adiponectin levels and adiponectin mRNA levels of adipose tissue were markedly decreased in L-NAME-treated rats. Cotreatment of pioglitazone (PIO) or allopurinol (ALL) with L-NAME restored plasma adiponectin concentration and fat adiponectin mRNA levels to control levels. Thus, adiponectin levels were decreased in L-NAME-treated rats, however, they returned to normal following administration of PIO due to transcriptional activation of the adiponectin gene, as well as administration of ALL, likely due to elimination of oxidative stress. Oxidative stress appears to be an important cause of hypoadiponectinemia.
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PMID:Hypoadiponectinemia is caused by chronic blockade of nitric oxide synthesis in rats. 2196 Nov 61

Vascular protection is key to reducing the morbidity associated with diabetes. Angiotensin II is known to exert a variety of deleterious effects on the vasculature, and this is likely to be a major explanation of the protective benefits observed with blockade of the renin-angiotensin-aldosterone system (RAAS). Intriguingly, RAAS blockade also appears to reduce the onset of new diabetes, which points to a fundamental effect on metabolism. Recent developments have thrown new light onto the mechanism of these effects. The importance of unopposed stimulation of the angiotensin II type 2 (AT(2)) receptor in vascular protection is recognised, and recent studies have revealed that some angiotensin II type 1 (AT(1)) receptor blockers (ARBs) show partial peroxisome proliferator-activated receptor-gamma (PPARgamma) agonistic activity in vitro, an effect that is at least partly due to direct interaction with PPARgamma itself. There is a clear order of potency among the ARBs, with telmisartan the most potent and the only ARB to show an effect at physiologically achievable plasma concentrations. Adiponectin, an adipokine closely involved with glucose sensitisation, is also modulated by the relative activation of AT(1) and AT(2) receptors. Such effects would suggest that important benefits may result from the use of ARBs in clinical practice, although confirmation of the clinical relevance will depend upon the results of numerous ongoing studies.
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PMID:Vascular protection in diabetes: a pharmacological view of angiotensin II type 1 receptor blockers. 1586 16

Obesity and its related disorders, glucose intolerance, hypertension and hyperlipidemia, collectively named the metabolic syndrome, result in substantial cardiovascular morbidity and mortality. Recent data point to several underlying regulatory mechanisms through which obesity links these various outcomes. Adipose tissue is now understood to function not merely as a passive energy storage depot but as an active endocrine organ, producing a variety of bioactive substances termed adipocytokines. Adiponectin, an adipocytokine first described as the most abundant protein produced by adipocytes, appears to serve as a central regulatory protein in many of the physiologic pathways controlling lipid and carbohydrate metabolism, and to mediate various vascular processes. Adiponectin displays both anti-inflammatory and antiatherogenic properties. Unlike other adipocytokines, its levels are paradoxically decreased in obesity and insulin-resistance states including metabolic syndrome and diabetes, as well as hypertension and coronary artery disease. This review will detail the relationship of adiponectin to various features of obesity and insulin-resistance syndromes, as well as its relationship to the cardiovascular complications of these disorders.
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PMID:Adiponectin: linking the metabolic syndrome to its cardiovascular consequences. 1588 74

Metabolic syndrome is thought to result from obesity and obesity-linked insulin resistance. Obesity in adulthood is characterized by adipocyte hypertrophy. Adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active "adipokines."Heterozygous peroxisome proliferator-activated receptor-gamma knockout mice were protected from high-fat diet induced obesity, adipocyte hypertrophy, and insulin resistance. Systematic gene profiling analysis of these mice revealed that adiponectin/Acrp30 was overexpressed. Functional analyses including generation of adiponectin transgenic or knockout mice have revealed that adiponectin serves as an insulin-sensitizing adipokine. In fact, obesity-linked down-regulation of adiponectin was a mechanism whereby obesity could cause insulin resistance and diabetes. Recently, we have cloned adiponectin receptors in the skeletal muscle (AdipoR1) and liver (AdipoR2), which appear to comprise a novel cell-surface receptor family. We showed that AdipoR1 and AdipoR2 serve as receptors for globular and full-length adiponectin and mediate increased AMP-activated protein kinase, peroxisome proliferator-activated receptor-alpha ligand activities, and glucose uptake and fatty-acid oxidation by adiponectin. Obesity decreased expression levels of AdipoR1/R2, thereby reducing adiponectin sensitivity, which finally leads to insulin resistance, the so-called "vicious cycle." Most recently, we showed that osmotin, which is a ligand for the yeast homolog of AdipoR (PHO36), activated AMPK via AdipoR in C2C12 myocytes. This may facilitate efficient development of adiponectin receptor agonists. Adiponectin receptor agonists and adiponectin sensitizers should serve as versatile treatment strategies for obesity-linked diseases such as diabetes and metabolic syndrome.
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PMID:Adiponectin and adiponectin receptors. 1589 98

Adiponectin is emerging as an important molecule in obesity, the metabolic syndrome, and cardiovascular disease. On the other hand, smoking habit is well known to be related to cardiovascular disease and hypertension. To examine the association between adiponectin concentration and smoking habit, we performed an epidemiological survey and an acute exposure test in humans and an experiment in adipocytes to elucidate the mechanism underlying the association between adiponectin and smoking. In the epidemiological study, we enrolled a total of 331 male subjects to examine chronic smoking exposure. Plasma adiponectin was significantly lower (P=0.01) in current smokers (5.3+/-0.3 microg/mL) than in never-smokers (6.5+/-0.4 microg/mL). A significant association between smoking and low adiponectin level was also confirmed in multiple regression analysis including age, body mass index, hypertension, diabetes, hyperlipidemia, and creatinine clearance (never-smokers 6.5+/-0.4 microg/mL; past smokers 5.6+/-0.3 microg/mL; current smokers 5.2+/-0.4 microg/mL; F=4.52; P=0.01). To examine the acute effect of smoking on adiponectin concentration for 12 hours, we measured plasma adiponectin level in 5 male never-smokers before smoking and 3, 6, and 12 hours after smoking, with the result that adiponectin showed a significant decrease after smoking (12 hours; -14.5+/-0.6%; P<0.01). In cultured mouse 3T3-L1 adipocytes, H2O2 and nicotine reduced the mRNA expression and secretion of adiponectin in a dose-dependent manner. Smoking habit is associated with adiponectin concentration in men, and its suppressive effect is mediated in part through direct inhibition of smoking on adiponectin expression in adipocytes.
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PMID:Association of hypoadiponectinemia with smoking habit in men. 1589 61

Adiponectin is an adipose-derived hormone that enhances insulin sensitivity and plays an important role in regulating energy homeostasis. Here, we demonstrate that the DNA encoding the first intron of the human adiponectin gene contains an intronic enhancer that regulates adiponectin gene expression in an adipose tissue-specific manner. Insertion of the DNA encoding the first intron into reporter constructs containing the proximal adiponectin promoter (Pro-Int1-Luc) resulted in a 20-fold increase in activity relative to the promoter alone in 3T3-L1 adipocytes. Coexpression of CCAAT/enhancer-binding protein (C/EBP)alpha increased luciferase activity of the Pro-Int1-Luc construct approximately 75-fold but had no effect on the constructs containing the proximal adiponectin promoter alone. At least eight potential C/EBPalpha response elements are located between +3000 to +10000 nucleotides within the DNA encoding the first intron, including a 34-bp core sequence for the intronic enhancer that contains three tandem C/EBPalpha response elements. However, the intronic enhancer is not conserved between human and mouse. Overexpression or siRNA-mediated knockdown of endogenous C/EBPalpha significantly increased or decreased, respectively, adiponectin mRNA levels in differentiated human Chub-S7 adipocytes, while neither C/EBPbeta nor C/EBPdelta significantly affected adiponectin expression in mature adipocytes. Thus, C/EBPalpha is a key transcription factor for full activation of human adiponectin gene transcription in mature adipocytes through interaction with response elements in the intronic enhancer.
Diabetes 2005 Jun
PMID:C/EBPalpha regulates human adiponectin gene transcription through an intronic enhancer. 1591 96

Adiponectin is an adipocytokine with antidiabetogenic properties. The present study investigated: (i) the effect of race on adiponectin levels and (ii) the relationship of adiponectin levels in children to insulin sensitivity and secretion. Fasting adiponectin levels were determined in 22 healthy prepubertal black compared with 22 white children of similar body composition. We previously reported these black children to have lower insulin sensitivity and higher first-phase insulin secretion than their white peers. Fasting adiponectin levels were lower in black children (9.9 +/- 1.0 microg/mL vs. 15.7 +/- 1.1 microg/mL, p < 0.001). Adiponectin correlated positively with insulin sensitivity (r = 0.29, p = 0.06) and negatively with first-phase insulin levels (r = -0.47, p = 0.001). In a multiple regression analysis, 48% of the variance in first-phase insulin secretion was explained by the independent effects of race (p = 0.017), adiponectin (p = 0.03), and percentage of body fat (p < 0.001). Adiponectin did not contribute significantly to the variance in insulin sensitivity. In summary, black children have approximately 35% lower adiponectin levels than their white peers. Lower adiponectin does not seem to explain the racial differences in insulin sensitivity. The relationship of hyperinsulinemia and hypoadiponectinemia needs to be further explored.
Pediatr Diabetes 2005 Jun
PMID:Does adiponectin explain the lower insulin sensitivity and hyperinsulinemia of African-American children? 1596 38

Adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2) are newly identified receptors for adiponectin, an adipocytokine with anti-inflammatory and insulin-sensitizing properties. We screened for polymorphisms by performing sequence analysis on all eight exons, splice junctions, and approximately 2 kb of the 5' flanking regions of each receptor. We detected 5 single nucleotide polymorphisms (SNPs) in ADIPOR1 and 16 SNPs in ADIPOR2. We genotyped these SNPs in Amish subjects with type 2 diabetes (n = 137), impaired glucose tolerance (IGT) (n = 139), and normal glucose tolerance (n = 342) to test for association with type 2 diabetes. Three intronic SNPs in ADIPOR1 were significantly associated with type 2 diabetes (P = 0.014-0.007; odds ratio [OR] 1.61-1.65) and in high linkage disequilibrium (r2 = 0.97-1.0). In ADIPOR2, we found that five SNPs delineated one large haplotype block (r2= 0.9-1.0) spanning >98 kb of the gene and promoter region, which was strongly associated with the combined type 2 diabetes/IGT trait (P < or = 0.001; OR 1.64-1.71). To our knowledge, these data provide the first evidence for association between variation in the adiponectin receptors and type 2 diabetes.
Diabetes 2005 Jul
PMID:Genetic variation in adiponectin receptor 1 and adiponectin receptor 2 is associated with type 2 diabetes in the Old Order Amish. 1598 28


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