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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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.
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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

The Adiponectin, an adipocytokine, is a plasma protein produced and secreted exclusively by adipose tissues. Adiponectin has important effects on angiocardiopathy, obesity and type 2 diabetes. In addition, adiponectin has certain roles in inflammation and hematopoiesis. Primarily results from adiponectin treatment of type 2 diabetes and some metabolism diseases suggest that adiponectin may serve as a potential and novel medicine.
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PMID:[Research advancement of adipocytokine adiponectin]. 1499 11

Adiponectin is an adipocytokine with insulin-sensitizing and antiatherogenic properties. Reduced concentrations of adiponectin precede the onset of type 2 diabetes and the development of atherosclerosis. Our aim was to quantify adiponectin concentrations in small for gestational age (SGA) children. Fifty-one SGA children, 24 obese, and 17 short-normal children with birth weight appropriate for gestational age (short-AGA) were studied. The statures of the SGA children were corrected for their midparental height and subdivided into two groups according to their corrected height: catch-up growth group, children with corrected height of 0 z-score or greater (n = 17); and noncatch-up growth group, subjects with corrected height less than 0 z-score (n = 34). SGA children showed adiponectin levels significantly lower than short- normal children (35.2 +/- 3.5 vs. 80.4 +/- 26.6 micro g/ml; P < 0.0001) and obese children (77.5 +/- 39.4 micro g/ml; P < 0.0001). Catch-up growth children showed adiponectin levels significantly lower than noncatch-up growth subjects (29.4 +/- 10.3 vs. 38.1 +/- 11.5 micro g/ml; P = 0.01). Adiponectin concentrations were inversely related to height z-score, corrected stature, weight, and body mass index and were positively related to birth weight. Our results suggest that adiponectin levels are reduced in SGA children and are even lower in those with postnatal catch-up growth. Whether this finding implies a higher risk of developing type 2 diabetes and atherosclerosis remains to be established.
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PMID:Adiponectin levels are reduced in children born small for gestational age and are inversely related to postnatal catch-up growth. 1500 32

Communication between adipose and other tissues has been hypothesized since at least the 1940s to be bidirectional. Despite this expectation, early progress was largely limited to adipose tissue's role in metabolism and storage of fatty acids, its development, and its response to endocrine and neural cues. However, efforts of the last decade have identified several molecules that are secreted from adipocytes, apparently for the purpose of signaling to other tissues. Cloning of the mouse obesity gene in 1994 is perhaps the most famous impetus for recognition that adipocytes are active in the regulation of multiple body functions. The product of this gene, leptin, has since been found to inhibit feeding, enhance energy expenditure, and stimulate gonadotropes. Evidence for the roles of other adipocyte-derived signals is being generated. Resistin is a protein that can cause whole-body insulin resistance. Its expression is correlated with body fatness and is inhibited by thiazolidinediones, perhaps mediating the association of type 2 diabetes with obesity, and the effectiveness of these drugs. Resistin and a related molecule, RELM alpha, can also inhibit differentiation of preadipocytes. Adiponectin/Acrp30 secretion from adipocytes is diminished in obese states. This protein can enhance use of fatty acids in lean tissues, inhibit glucose production by liver, and consequently decrease both blood glucose and BW. Adiponectin may also be responsible for the effectiveness of thiazolidinediones, given that these drugs promote adiponectin secretion. Secretion of complement proteins has been observed in adipocytes, and these interact to generate a signal called acylation-stimulating protein, which can promote triacylglycerol synthesis. These signals seem to be largely unique to adipocytes. Other signals are derived from adipose tissue, and it is unlikely that all the adipocyte's endocrine signals have been identified. Certainly, there is much to learn about how these signals function; however, it is clear that these biomedical research discoveries comprise a useful model for our study of growth and development in livestock.
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PMID:The adipocyte as an endocrine cell. 1503 52

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.
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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

Low plasma adiponectin has been identified as a risk factor for type 2 diabetes. Our objective was to determine the extent to which low maternal plasma adiponectin is predictive of gestational diabetes mellitus (GDM), a condition that is biochemically and epidemiologically similar to type 2 diabetes. We used a prospective, nested case-control study design to compare maternal plasma adiponectin concentrations in 41 cases with 70 controls. Subjects were selected from a population of 968 women who provided blood samples in early pregnancy. Plasma adiponectin was determined using an ELISA. Adiponectin concentrations were statistically significantly lower in women with GDM than controls (4.4 vs. 8.1 micro g/ml, P < 0.001). Approximately 73% of women with GDM, compared with 33% of controls, had adiponectin concentrations less than 6.4 micro g/ml. After adjusting for confounding, women with adiponectin concentrations less than 6.4 micro g/ml experienced a 4.6-fold increased risk of GDM, as compared with those with higher concentrations (95% confidence interval, 1.8-11.6). Our findings are consistent with other reports suggesting an association between hypoadiponectemia and risk of type 2 diabetes. Our findings extend the literature to include GDM. Studies designed to examine the effect of dietary and pharmacological mediators of adiponectin concentrations in pregnant and nonpregnant subjects are warranted.
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PMID:Plasma adiponectin concentrations in early pregnancy and subsequent risk of gestational diabetes mellitus. 1512 57

Adiponectin has been identified as one of the "adipocytokines" that are derived only from adipose tissue, and are abundantly present in circulating blood. Adiponectin has protective actions in the initiation and progression of atherosclerosis through anti-inflammatory and anti-atherogenic effects. Adiponectin levels are decreased in obesity, type 2 diabetes, and patients with coronary artery disease (CAD). Adiponectin levels were negatively correlated with the CRP levels in patients with CAD. Adiponectin plays a crucial role in the association between obesity, type 2 diabetes, and insulin resistance. Mechanisms explaining the relationship between adiponectin and insulin resistance suggest that adiponectin and tumor necrosis factor (TNF)-alpha inhibited each other's expression and production in adipocytes. Thiazolidinediones, which are insulin-sensitizing agents, increased the production of adiponectin through directly enhancing its gene expression. The C-terminal globular domain of adiponectin may play a central role in the protective effects against atherosclerosis. Adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) are expressed ubiquitously in most organs, especially in skeletal muscle in AdipoR1, and liver in AdipoR2. With the prospect of future basic and clinical research on the molecular structure-receptor relationship, adiponectin could become a promising target for future investigations in reducing the morbidity and mortality of atherosclerotic disease.
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PMID:Adiponectin and atherosclerotic disease. 1514 66

Insulin resistance is characterized by a peripheral resistance to insulin-mediated glucose uptake, and an hepatic resistance of glucose production to insulin. Insulin resistance in skeletal muscle is of a particular importance, and could be the consequence of an increase in intracellular and circulating fatty acids and triglycerides. Adipose tIssue plays an important role to regulate mobilization and release of fatty acids. Adipose tIssue is an endocrine organ which secretes several factors, including adiponectin. Adiponectin improves insulin sensitivity in skeletal muscle and liver, through a stimulation of fatty acid oxidation and glucose utilization. Thiazolidinediones enhance adiponectin expression and synthesis through PPARgamma, although the precise mechanism remains controversial. AMP-activated protein kinase (AMPK) is the main adiponectin target. Adiponectin, clearly, is a major modulator of glucose and lipid metabolism in insulin-sensitive tIssue and/or regulator of insulin-sensitivity, in obese and/or glucose intolerant subjects, as well as in type 2 diabetes mellitus. Recent works and the links between insulin resistance, adipose tIssue, adiponectin and its PPARgamma-enhanced secretion are reviewed in this paper.
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PMID:[Adiponectin: from adipocyte to skeletal muscle]. 1516 22

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


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