Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by interactions of genetic factors such as SNPs in the Adiponectin gene and environmental factors causing obesity, appears to play an important causal role in insulin resistance, type 2 diabetes, and the metabolic syndrome, which are linked to obesity. The adiponectin receptors, AdipoR1 and AdipoR2, which mediate the antidiabetic metabolic actions of adiponectin, have been cloned and are downregulated in obesity-linked insulin resistance. Upregulation of adiponectin is a partial cause of the insulin-sensitizing and antidiabetic actions of thiazolidinediones. Therefore, adiponectin and adiponectin receptors represent potential versatile therapeutic targets to combat obesity-linked diseases characterized by insulin resistance. This Review describes the pathophysiology of adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome.
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PMID:Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. 1682 76

Adiponectin, an adipocyte-specific plasma protein, has been reported to exhibit protective effects against atherosclerosis as well as an insulin-sensitizing effect. This study was designed to investigate the effect of adiponectin on carotid arterial stiffness in type 2 diabetic patients treated with pioglitazone and metformin. Twenty type 2 diabetic patients were enrolled and divided into 2 groups, a pioglitazone-treated group (n = 10) and a metformin-treated group (n = 10). Before and after intervention, plasma adiponectin levels were measured by enzyme-linked immunosorbent assay and carotid arterial stiffness was evaluated by the stiffness parameter beta, measured by ultrasound equipped with a phase-locked echo-tracking system. In the pioglitazone group, plasma adiponectin level significantly increased and stiffness parameter beta significantly decreased, whereas in the metformin group neither of these parameters changed significantly. The changes in stiffness parameter beta were significantly and inversely correlated with change in plasma adiponectin level after treatment with pioglitazone or metformin in the group of all subjects (r = -0.472, P = .036). In conclusion, the present study is the first to demonstrate that increase in adiponectin level after treatment with the insulin sensitizers pioglitazone and metformin may improve arterial stiffness in patients with type 2 diabetes mellitus.
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PMID:Effect of adiponectin on carotid arterial stiffness in type 2 diabetic patients treated with pioglitazone and metformin. 1683 32

Adiponectin, an adipocyte-secreted protein, is known to have anti-atherogenic, anti-inflammatory and anti-diabetic properties and its serum levels are decreased in obesity, type 2 diabetes, and coronary artery disease. Several studies have been performed to investigate the association of genetic variations in the adiponectin with obesity, insulin resistance, and type 2 diabetes, but few studies were performed in association with coronary artery disease. Therefore we examined the associations between two single nucleotide polymorphisms (SNPs), +45T>G and +276G>T of the adiponectin gene, and coronary artery diseases (CAD). One hundred and fifty six subjects (mean age 57.4 yrs) were enrolled in which coronary angiograms were performed due to chest pain. Genotypings were done for two SNPs in the adiponectin gene by Taqman polymerase chain reaction (PCR) method. The presence of CAD was defined as a >50% reduction of coronary artery diameter. Among 156 subjects, the allele frequencies were 0.683 for G allele and 0.317 for T allele in SNP +276G>T and 0.705 for T allele and 0.295 for G allele in SNP +45T>G. Both genotypes were in compliance with Hardy-Weinberg equilibrium. No association with the presence of CAD was observed for adiponectin gene SNP276 and SNP45 (p = 0.954, p = 0.843). Also, no significant association was observed between the severity of CAD and either SNPs (p = 0.571, p = 0.955). Our study showed that SNP +276G>T and +45T>G in adiponectin gene were not associated with the presence of CAD. Further studies will be necessary to confirm the role of SNP 276G>T and 45T>G in the development of CAD.
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PMID:Associations between two single nucleotide polymorphisms of adiponectin gene and coronary artery diseases. 1692 24

Adiponectin, which is encoded by the ADIPOQ gene, has been shown to modulate insulin sensitivity and glucose homeostasis. Plasma adiponectin levels are decreased in type 2 diabetes and obesity. Genetic variations within the ADIPOQ gene are associated with decreased adiponectin hormone levels. To analyze specific single-nucleotide polymorphisms (SNPs) and their association with T2D, 365 German subjects with T2D and 323 control subjects were screened. Three common SNPs - +45T>G in exon 2, and 2 promoter variants SNPs -11391G>A and -11377C>G - were analyzed. We found that the variant allele of SNP -11391G>A was significantly more frequent in the diabetic patient group than in the control group (p=0.003). Carrying the haplotype of SNP -11391A and SNP -11377C was associated with a 1.50-fold (p=0.03) increase in diabetes risk. The combination of the A-C haplotype and the G-C haplotype was associated with significantly elevated diabetes risk (OR=2.82 (95% CI: 1.35-5.91), p=0.006) after correction for BMI and age. Our observations suggest that diploid combinations of haplotype in the adiponectin gene promoter region contribute to the genetic risk of T2D in individuals from a German Caucasian population.
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PMID:Haplotypes in the promoter region of the ADIPOQ gene are associated with increased diabetes risk in a German Caucasian population. 1693 80

Adiponectin, an adipokine facilitating insulin action, has antiatherogenic effects. This study investigated whether common polymorphisms in the adiponectin receptor 1 (ADIPOR1) gene mediating these effects influence the risk of coronary artery disease (CAD) in type 2 diabetes. Linkage disequilibrium analysis of 28 single nucleotide polymorphisms (SNPs) spanning the entire ADIPOR1 locus revealed two haplotype blocks that could be tagged by six SNPs. These six markers were typed in two populations of CAD-positive and -negative subjects with type 2 diabetes, one from Boston (n = 411) and the other from Italy (n = 533). In the Boston population, the three tags of the more 3' block were all significantly associated with CAD (P = 0.001-0.01). A similar trend, although not significant, was found in Italian subjects. Haplotype analysis of the combined populations revealed different haplotype distributions in case and control subjects (P = 0.0002), with one common haplotype being associated in homozygotes with a greater than threefold increase in cardiovascular risk (odds ratio 3.6 [95% CI 1.8-7.2]). Some of the genotypes associated with increased cardiovascular risk were associated with 30-40% lower ADIPOR1 mRNA levels in blood mononuclear cells (n = 60) and adipose tissue biopsies (n = 28) (P = 0.001-0.014). Our findings point to genetic variability at the ADIPOR1 locus as a strong determinant of CAD susceptibility in type 2 diabetes.
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PMID:Common haplotypes at the adiponectin receptor 1 (ADIPOR1) locus are associated with increased risk of coronary artery disease in type 2 diabetes. 1700 41

Adiponectin levels are significantly lower in obese adult patients with type 2 diabetes mellitus, essential hypertension, dyslipidemia, and cardiovascular disease. However, the role of hypoadiponectinemia in nonobese healthy adults has not been fully elucidated. In this study, we examined the association between hypoadiponectinemia and cardiovascular risk factors and estimated plasma adiponectin values in nonobese, apparently healthy adults. A total of 204 male and 214 female healthy individuals aged 20 to 80 years, with a body mass index (BMI) of less than 25 kg/m2, were included in this study. We measured patients' plasma adiponectin levels, serum lipid profiles, high-sensitivity C-reactive protein (hs-CRP) levels, fasting glucose levels, and fasting insulin levels. Mean values of plasma adiponectin were 5.45 +/- 3.3 microg/mL in male and 8.16 +/- 4.6 microg/mL in female subjects. The hypoadiponectinemia group (< 4.0 microg/mL) had significantly higher levels (P < .01) of BMI, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglycerides, but lower levels of high-density lipoprotein cholesterol (HDL-C). In males, plasma adiponectin levels were inversely correlated with BMI (r = -0.32, P < .01), HOMA-IR (r = -0.14, P < .05), triglyceride levels (r = -0.17, P < .05), and hs-CRP levels (r = -0.15, P < .05), and positively correlated with HDL-C (r = 0.24, P < .01). In females, plasma adiponectin levels were negatively correlated with BMI (r = -0.31, P < .01), fasting glucose (r = -0.18, P < .01), fasting insulin (r = -0.23, P < .01), HOMA-IR (r = -0.24, P < .01), and triglyceride (r = -0.18, P < .01) levels, and positively correlated with HDL-C (r = 0.37, P < .01). Sex, age, BMI, and HDL-C (P < .01 for each) were found to be independent factors associated with plasma adiponectin levels in multivariate analysis. Hypoadiponectinemia is significantly associated with cardiovascular risk factors such as insulin resistance and atherogenic lipid profiles in nonobese, apparently healthy subjects.
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PMID:Association between hypoadiponectinemia and cardiovascular risk factors in nonobese healthy adults. 1704 59

Adiponectin, a novel adipocytokine produced exclusively in the adipose tissue, plays a major role in the development of metabolic syndrome, type 2 diabetes mellitus, and related cardiovascular (CV) diseases. However, information is scant regarding the association of adiponectin with measures of CV risk in young adults. This aspect was examined in a biracial (black-white) community-based sample of 1153 individuals (mean age, 36.2 years; 70% white, 43% male) who participated in the Bogalusa Heart Study. Adiponectin levels showed race (white > black, P < .0001) and sex (female > male, P < .0001) differences, and correlated significantly in a beneficial manner to measures of obesity (body mass index, waist circumference, and abdominal height), mean arterial blood pressure, lipoprotein variables (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), measures of glucose homeostasis (insulin, glucose, homeostasis model assessment of insulin resistance [HOMA-IR]), and uric acid, after adjusting for age, race, sex, and cigarette smoking. In multivariate analysis that used either body mass index or abdominal height as a measure of general and visceral adiposity in 2 separate models, HOMA-IR was the major contributor explaining 18.4% and 18.1% of the variance, respectively. There was a significant interaction between abdominal height and HOMA-IR on adiponectin level in that the inverse association between adiponectin and insulin resistance was pronounced at higher level of visceral adiposity. Furthermore, adiponectin levels decreased with increasing number of metabolic syndrome risk factors defined by the National Cholesterol Education Program Adult Treatment Panel III (P for trend <.0001). Moreover, adiponectin levels were low among those with positive parental histories of coronary heart disease (P = .03), hypertension (P = .04), and type 2 diabetes mellitus (P = .01), considered as surrogate measures of risk. These findings, by showing an inverse association of adiponectin with insulin resistance, visceral adiposity, and related metabolic syndrome, and also with positive parental histories of coronary heart disease, hypertension, and type 2 diabetes mellitus, underscore the value of adiponectin in CV and type 2 diabetes mellitus risk assessments in young adults.
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PMID:Adiponectin and its correlates of cardiovascular risk in young adults: the Bogalusa Heart Study. 1704 60

Nifedipine, a dihydropyridine calcium antagonist, improves endothelial function in patients with hypercholesterolaemia by enhancing nitric oxide (NO) activity, and increases endothelial NO bioavailability by antioxidant mechanisms. We administered a long-acting nifedipine formulation (controlled release (CR) nifedipine: 20 mg/day) to hypertensive patients for 6 months. There were no other changes of drug treatment during therapy with CR nifedipine. Clinical and biochemical data obtained before and after CR nifedipine administration were compared. All markers were measured by enzyme-linked immunosorbant assay. The levels of soluble markers (soluble CD40 ligand, soluble P-selectin, and soluble E-selectin), microparticles (MP) (platelet-derived MP, monocyte-derived MP, and endothelial cell-derived MP), and adiponectin differed between the control group and the hypertension group. The levels of these markers were also different in hypertensive patients with and without type 2 diabetes compared with the control group. In the hypertensive patients with type 2 diabetes, all markers except adiponectin decreased significantly after 3 months of CR nifedipine treatment. In contrast, markers were unchanged in the hypertensive patients without type 2 diabetes. Adiponectin was increased after 6 months of CR nifedipine treatment in hypertensive patients with type 2 diabetes. The effects of CR nifedipine on platelet/monocyte activation and adiponectin levels demonstrated in the present study indicate the potential effectiveness of calcium antagonist therapy for hypertensive patients with type 2 diabetes.
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PMID:Effect of nifedipine on adiponectin in hypertensive patients with type 2 diabetes mellitus. 1706 83

Insulin resistance is the principal cause of glucose intolerance and type 2 diabetes and induces progression of severe atherosclerosis in these patients. Adiponectin, the adipose-specific proteins, is known to correlate negatively with insulin resistance in patients with obesity and type 2 diabetes. The purpose of this study was to evaluate the potential of using serum adiponectin levels as a marker of insulin resistance in various states of insulin resistance. Furthermore, we attempted to establish a modified index of the homeostasis model assessment index (HOMA-IR), calculated from the product of serum insulin and plasma glucose levels divided by serum adiponectin levels (HOMA-AD). We recruited 117 Japanese subjects with various degrees of glucose tolerance and determined serum adiponectin levels and insulin sensitivity (M-value) by using the euglycemic hyperinsulinemic clamp technique. M-value, the gold standard index of insulin resistance, correlates significantly and independently with fasting insulin (r=-0.313, P<0.001), glucose (r=-0.319, P<0.001), and adiponectin (r=0.241, P<0.002) levels. M-values were more significantly correlated with HOMA-AD (r=-0.643, P<0.001) than HOMA-IR values (r=-0.591, P<0.001). In subjects with moderate hyperglycemia (fasting glucose levels>8.0mmol/L, n=30), HOMA-AD showed a more significant correlation with the M-value than HOMA-IR (r=-0.535, P=0.005 versus r=-0.461, P=0.010). We would therefore like to propose a novel index, HOMA-AD, as a simple and adequate index for determining insulin resistance even in diabetic patients with overt hyperglycemia.
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PMID:A novel index of insulin resistance determined from the homeostasis model assessment index and adiponectin levels in Japanese subjects. 1708 46

Adiponectin is an adipose-derived hormone that plays an important role in maintaining energy homeostasis. Adiponectin gene expression is diminished in both obesity and type 2 diabetes. However, the mechanism underlying the impaired adiponectin gene expression remains poorly understood. Recent studies have indicated that forkhead transcription factor O1 (Foxo1) and silent information regulator 2 mammalian ortholog SIRT1 are involved in adipogenesis. Here we have shown that Foxo1 up-regulates adiponectin gene transcription through a Foxo1-responsive region in the mouse adiponectin promoter that contains two adjacent Foxo1 binding sites. Foxo1 interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to form a transcription complex at the mouse adiponectin promoter and up-regulates adiponectin gene transcription. Our study has revealed that C/EBPalpha accesses the adiponectin promoter through two Foxo1 binding sites and acts as a co-activator. Further, SIRT1 increases adiponectin transcription in adipocytes by activating Foxo1 and enhancing Foxo1 and C/EBPalpha interaction. Importantly, both Foxo1 and SIRT1 protein levels were significantly lower in epididymal fat tissues from db/db and high fat diet-induced obese mice compared with normal mice. We propose that low expression of SIRT1 and Foxo1 leads to impaired Foxo1-C/EBPalpha complex formation, which contributes to the diminished adiponectin expression in obesity and type 2 diabetes.
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PMID:SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein alpha transcriptional complex. 1709 May 32


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