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

Adiponectin is an adipocyte-derived hormone best known for its insulin-sensitizing ability. The expression and circulating concentration of adiponectin are decreased in type 2 diabetics and increase following treatment with thiazolidinediones. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide whose levels are elevated in numerous disease states, including obesity and diabetes. ET-1 has profound effects on adipose tissue metabolism and alters the release of adipose-derived factors such as leptin and resistin, therefore we investigated the role of ET-1 in adiponectin secretion. 3T3-L1 adipocytes were treated with insulin (100 nM), ET-1 (100 nM), or the appropriate vehicle and adiponectin secretion into the media was determined by immunoblotting and densitometric analysis. Adiponectin secretion significantly increased 1h following insulin or ET-1 treatment, respectively. Pretreatment with ET-1 for 24h significantly inhibited the ability of insulin or ET-1 to acutely stimulate adiponectin secretion. The specific ET(A) receptor antagonist, BQ-610 (1 microM), significantly inhibited ET-1-stimulated adiponectin secretion. In summary, ET-1 acutely stimulates adiponectin secretion through the ET(A) receptor. Chronic exposure to ET-1 dramatically decreases the stimulatory effect of insulin and ET-1 on adiponectin secretion. Our findings suggest vascular factors such as ET-1 may play a role in the regulation of adiponectin secretion and whole body energy metabolism.
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PMID:Regulation of adiponectin secretion by endothelin-1. 1465 62

Adiponectin/Acrp30 is a fat cell-specific secretory product. The convergence of results from epidemiological, pharmacological and genetic studies over the last 2 yr has highlighted the important role that this multimeric protein complex plays in the context of insulin sensitivity. While the exact mechanism of action has not been elucidated, it is clear that adiponectin has insulin-sensitizing effects on both liver and muscle. The important role that adipose tissue plays in energy homeostasis as a storage compartment for triglycerides has been appreciated for a long time. The identification of leptin as a key hormone involved in central control of energy metabolism suggested that adipocytes also use polypeptide hormones to influence metabolic processes at distant sites. The recent progress made towards the characterization of the physiological role of adiponectin highlights the important role of adipose tissue as an endocrine organ and its central role in the fine-tuning of hepatic and muscle insulin responsiveness.
Pediatr Diabetes 2003 Mar
PMID:Adiponectin/Acrp30, an adipocyte-specific secretory factor: physiological relevance during development. 1465 22

The adipose tissue produces and secretes many bioactive substances, which we conceptualized as Adipocytokines (Nature Medicine 1996). Adiponectin is a novel adipocytokine, which we identified by screening the adipose-specific genes from human fat. Adiponectin is a secreted protein, the concentration of which reaches as high as 5-15 micrograms/ml in human plasma. Adiponectin mRNA is expressed exclusively in adipose tissues. The adiponectin mRNAs and its plasma levels are reduced in obesity, type 2 diabetes and atherosclerosis. Hyperinsulinemic euglycemic clamp studies in humans and monkeys, and several recent studies from others revealed that adiponectin is an insulin-sensitizing hormone. Furthermore, adiponectin exhibited anti-atherogenic moieties, decreasing the attachment of monocytes to endothelial cells through inhibiting the expression levels of adhesion molecules. It reduced the lipid accumulation in macrophages through reducing the expression of scavenger receptor, and inhibited the cytokine-stimulated proliferation of smooth muscle cells. The genetic mutation of the adiponectin gene accompanying hypoadiponectinemia was strongly associated with the incidence of type 2 diabetes and atherosclerosis in Japanese subjects. Hypoadiponectinemia was the strongest predictor for the development of type 2 diabetes in humans. Adiponectin knockout mice exhibited diet-induced diabetes and severer atherosclerotic response by vascular injury. Adiponectin supplement reversed the insulin resistance syndrome including diabetes and atherosclerotic change in the knockout mice. We conclude that "Hypoadiponectinemia" stands upstream of the pathophysiology of metabolic syndrome, hence, can be a direct target of drug intervention to tackle life style-related disease rampant in developed countries.
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PMID:[Adipocytokines and life style-related disease]. 1467 87

Genome-wide scanning is a powerful tool to identify susceptible chromosome loci, however, individual chromosomal regions still have many candidate genes. Although cDNA microarray analysis provides valuable information for identifying genes involved in pathogenesis, expression levels of many genes are changed. A novel approach for identification of therapeutic targets is the combination of genome-wide scanning and the use of DNA chips, as shown in Fig. (1). Using DNA chips, we screened for secreted molecules, the expressions of which were changed in adipose tissues from mice rendered insulin resistance. Decreased expression of one of these molecules, adiponectin/Acrp30, correlates strongly with insulin resistance. Interestingly, recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where adiponectin gene is located. Decreasing serum adiponectin levels are associated with increased risk for type 2 diabetes. Interestingly, adiponectin was decreased in insulin resistant rodent models both of obesity and lipoatrophy, and replenishment of adiponectin ameliorated their insulin resistance. Moreover, adiponectin transgenic mice ameliorated insulin resistance and diabetes Adiponectin knockout mice showed insulin resistance and glucose intolerance. In muscle and liver, adiponectin activated AMP kinase and PPARalpha pathways thereby increasing beta-oxidation of lipids, leading to decreased TG content, which ameliorated insulin resistance under a high-fat diet. Despite similar plasma glucose and lipid levels on an apoE deficient background, adiponectin transgenic apoE deficient mice showed amelioration of atherosclerosis, which was associated with decreased expressions of class A scavenger receptor and tumor necrosis factor alpha. Finally, cDNA encoding adiponectin receptors (AdipoR1 and R2) have been identified by expression cloning, which facilitates the understanding of molecular mechanisms of adiponectin actions and obesity-linked diseases such as diabetes and atherosclerosis and the designing of novel antidiabetic and anti-atherogenic drugs with AdipoR1 and R2 as molecular targets.
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PMID:Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine. 1468 55

The aim of this study was to investigate the relationship between adiponectin and leptin and body fat distribution. One hundred and ninety-seven women participated in this study. Subjects were grouped based on their visceral adipose tissue area (VAT). Body fat distribution was determined by computed tomography. The numbers in the subcutaneous fat dominant group (SFDG) and visceral fat dominant group (VFDG) were 79 and 118, respectively. The VFDG showed lower adiponectin levels than the SFDG (8.9+/-0.4 microg/ml versus 11.4+/-0.7 microg/ml, P=0.006), but leptin levels did not differ significantly between groups (18.8+/-1.1 ng/ml versus 17.7+/-1.8 ng/ml, P=0.111). Adiponectin levels were inversely correlated with fasting insulin, HOMA-IR, triglyceride, SBP and DBP, subcutaneous adipose tissue area (SAT) and VAT, and waist-to-hip ratio (WHR). Leptin levels were positively correlated with fasting glucose and insulin, HOMA-IR, triglyceride, SBP and DBP, VAT and SAT, and WHR (all values of P<0.05). VAT and HDL-cholesterol were independent variables of adiponectin concentrations (R(2)=0.207, P<0.0001), and SAT, fasting insulin, and HOMA-IR were independent variables of leptin concentrations (R(2)=0.498, P<0.0001) In conclusion, adiponectin and leptin concentrations, although associated with metabolic parameters, were more strongly influenced by VAT in the case of adiponectin, and by SAT in the case of leptin.
Diabetes Res Clin Pract 2004 Feb
PMID:Relationship between serum adiponectin and leptin concentrations and body fat distribution. 1473 54

Adiponectin (APM1) is an adipocyte-derived peptide. The APM1 gene is located on chromosome 3q27 and linked to type 2 diabetes. In patients with type 2 diabetes, the adiponectin level in plasma is decreased in comparison to healthy subjects. To identify genetic defects of the APM1 gene that contribute to the development of type 2 diabetes, we genotyped 13 single nucleotide polymorphisms (SNPs) in 106 patients with type 2 diabetes, 325 patients with impaired glucose tolerance (IGT), and 497 nondiabetic control subjects in Swedish Caucasians by using dynamic allele-specific hybridization (DASH). We found that SNPs -11426(A/G) and -11377(G/C) in the proximal promoter region had significant differences of allele frequencies between type 2 diabetic patients and nondiabetic control subjects (P = 0.02 and P = 0.04, respectively). SNP-11426(A/G) was significantly associated with fasting plasma glucose in type 2 diabetic patients (P = 0.02) and in IGT subjects (P = 0.04), while the patients carrying CC and CG genotypes for SNP-11377(G/C) had a higher BMI than the patients with the GG genotype (P = 0.03). Haplotype analysis of 13 SNPs in the APM1 gene showed that estimates of haplotype frequencies in Swedish Caucasians are similar to those estimated in French Caucasians. However, no significant association of haplotypes with type 2 diabetes and IGT was detected in our study. The present study provides additional evidence that SNPs in the proximal promoter region of the APM1 gene contribute to the development of type 2 diabetes.
Diabetes 2004 Feb
PMID:Single nucleotide polymorphisms in the proximal promoter region of the adiponectin (APM1) gene are associated with type 2 diabetes in Swedish caucasians. 1474 63

Hormones produced by adipose tissue play a critical role in the regulation of energy intake, energy expenditure, and lipid and carbohydrate metabolism. This review will address the biology, actions, and regulation of three adipocyte hormones-leptin, acylation stimulating protein (ASP), and adiponectin-with an emphasis on the most recent literature. The main biological role of leptin appears to be adaptation to reduced energy availability rather than prevention of obesity. In addition to the well-known consequences of absolute leptin deficiency, subjects with heterozygous leptin gene mutations have low circulating leptin levels and increased body adiposity. Leptin treatment dramatically improves metabolic abnormalities (insulin resistance and hyperlipidemia) in patients with relative leptin deficiency due to lipoatrophy. Leptin production is primarily regulated by insulin-induced changes of adipocyte metabolism. Dietary fat and fructose, which do not increase insulin secretion, lead to reduced leptin production, suggesting a mechanism for high-fat/high-sugar diets to increase energy intake and weight gain. ASP increases the efficiency of triacylglycerol synthesis in adipocytes leading to enhanced postprandial lipid clearance. In mice, ASP deficiency results in reduced body fat, obesity resistance, and improved insulin sensitivity. Adiponectin production is stimulated by thiazolidinedione agonists of peroxisome proliferator-activated receptor-gamma and may contribute to increased insulin sensitivity. Adiponectin and leptin cotreatment normalizes insulin action in lipoatrophic insulin-resistant animals. These effects may be mediated by AMP kinase-induced fat oxidation, leading to reduced intramyocellular and liver triglyceride content. The production of all three hormones is influenced by nutritional status. These hormones, the pathways controlling their production, and their receptors are promising targets for managing obesity, hyperlipidemia, and insulin resistance.
Diabetes 2004 Feb
PMID:Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. 1474 80

Adiponectin may have an antiatherogenic effect by reducing endothelial activation. We hypothesized that plasma adiponectin levels were correlated with endothelial function. Plasma adiponectin level was determined by an in-house RIA assay using a rabbit polyclonal antibody in 73 type 2 diabetic patients and 73 controls. Endothelium-dependent and independent vasodilation of the brachial artery was measured by high-resolution vascular ultrasound. Plasma adiponectin level was lower in diabetic patients than in controls (4.73 +/- 1.96 vs. 7.69 +/- 2.80 microg/ml, respectively; P < 0.001), and they also had impaired endothelium-dependent (5.6 +/- 3.6 vs. 8.6 +/- 4.5%, respectively; P < 0.001) and -independent vasodilation (13.3 +/- 4.9 vs. 16.5 +/- 5.6%, respectively; P < 0.001). Plasma adiponectin correlated with endothelium-dependent vasodilation in controls (P = 0.02) and diabetic patients (P = 0.04). On general linear-model univariate analysis, brachial artery diameter, the presence of diabetes, plasma adiponectin, and high-density lipoprotein were significant independent determinants of endothelium-dependent vasodilation. In vitro experiments showed that endothelial cells expressed adiponectin receptors, and adiponectin increased nitric oxide production in human aortic endothelial cells. In conclusion, low plasma adiponectin level is associated with impaired endothelium-dependent vasodilation, and the association is independent of diabetes mellitus. Adiponectin may act as a link between adipose tissue and the vasculature.
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PMID:Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. 1476 94

Obesity is a risk factor for the development of many severe human diseases such as cardiovascular disorders, diabetes, and cancer, which are tightly linked to angiogenesis. The adipose tissue produces several growth factors/hormones including leptin, tumor necrosis factor alpha, and adiponectin. It has been found that adiponectin levels are reduced in obesity. Here, we report a unique function of adiponectin as a negative regulator of angiogenesis. In vitro, adiponectin potently inhibits endothelial cell proliferation and migration. In the chick chorioallantoic membrane and the mouse corneal angiogenesis assays, adiponectin remarkably prevents new blood vessel growth. Further, we demonstrate that the antiendothelial mechanisms involve activation of caspase-mediated endothelial cell apoptosis. Adiponectin induces a cascade activation of caspases-8, -9, and -3, which leads to cell death. In a mouse tumor model, adiponectin significantly inhibits primary tumor growth. Impaired tumor growth is associated with decreased neovascularization, leading to significantly increased tumor cell apoptosis. These data demonstrate induction of endothelial apoptosis as an unique mechanism of adiponectin-induced antiangiogenesis. Adiponectin, as a direct endogenous angiogenesis inhibitor, may have therapeutic implications in the treatment of angiogenesis-dependent diseases.
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PMID:Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. 1498 34

The plasma concentration of the adipocyte-derived peptide adiponectin is decreased in patients with obesity and type 2 diabetes. The adiponectin gene is located on chromosome 3q27, where a diabetes susceptibility locus has been mapped. Adiponectin gene polymorphisms (single nucleotide polymorphisms [SNPs]) have been associated with BMI, insulin sensitivity, and type 2 diabetes in some cross-sectional studies. Our aim was to assess the contribution of these SNPs in the development of features of the insulin resistance syndrome in a 3-year prospective study in approximately 4,500 French Caucasian subjects from the Epidemiologic Data on the Insulin Resistance Syndrome (DESIR) cohort. For subjects who were normoglycemic at baseline, the 3-year risk of becoming hyperglycemic (diabetes or impaired fasting glucose) was affected by two SNPs: G-11391A and T45G. For G-11391A, the risk was increased in GA carriers (odds ratio [OR] adjusted for sex [versus GG] = 1.60 [95% CI 1.16-2.20]; P = 0.004). For T45G, it was increased in GG carriers (OR [versus TT] = 2.71 [1.31-5.60]; P = 0.007). After 3 years, GG subjects had a greater increase in BMI (P = 0.009) and waist-to-hip ratio (P = 0.007). Adiponectin levels at baseline were associated with the development of hyperglycemia (P = 0.005), but the predictive effects on the risk for hyperglycemia were independent of adiponectin genotypes. In conclusion, in the DESIR study, variations at the adiponectin locus affect body weight gain, body fat distribution, and onset of hyperglycemia, as well as adiponectin levels. Adiponectin gene SNPs may have several phenotypic effects that co-occur with the development of the metabolic syndrome.
Diabetes 2004 Apr
PMID:Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study. 1504 34


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