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)

Angiopoietin-like protein 4 (ANGPTL4) represents an adipokine with metabolic effects within adipose tissue, such as inhibition of lipoprotein lipase activity and stimulation of lipolysis. These effects were convincingly demonstrated in mice. Therefore, we asked whether genetic variation within the ANGPTL4 gene contributes to prediabetic phenotypes, such as dyslipidemia, insulin resistance, or beta-cell dysfunction, in white subjects at an increased risk for type 2 diabetes mellitus. We genotyped 629 subjects with and without a family history of diabetes for the 4 single nucleotide polymorphisms (SNPs) rs4076317, rs2278236, rs1044250, and rs11672433 and performed correlational analyses with metabolic traits. For metabolic characterization, all subjects underwent an oral glucose tolerance test; a subset was additionally characterized by hyperinsulinemic-euglycemic clamp. The 4 SNPs rs4076317, rs2278236, rs1044250, and rs11672433 cover 100% of common genetic variation (minor allele frequency>or=0.05) within the ANGPTL4 gene (r2>or=0.8). None of these SNPs revealed significant correlation with anthropometric data (sex, age, body mass index, body fat, and waist-hip ratio) or with family history of diabetes. Furthermore, no reliable correlations were found with fasting triglycerides, fasting nonesterified fatty acids, and area under the curve of nonesterified fatty acids during oral glucose tolerance test or with parameters of insulin sensitivity and insulin secretion. Finally, haplotype analysis revealed the existence of 8 common diplotypes. None of these, however, was significantly correlated with insulin sensitivity, insulin secretion, or plasma lipid measures. We conclude that common genetic variation within the ANGPTL4 gene may not play a major role in the development of prediabetic phenotypes in our white population.
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PMID:Genetic variation within the ANGPTL4 gene is not associated with metabolic traits in white subjects at an increased risk for type 2 diabetes mellitus. 1844 26

Apelin is a bioactive peptide known as the ligand of the G protein-coupled receptor APJ. Diverse active apelin peptides exist under the form of 13, 17 or 36 amino acids, originated from a common 77-amino-acid precursor. Both apelin and APJ mRNA are widely expressed in several rodent and human tissues and have functional effects in both the central nervous system and peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular functions, fluid homeostasis, vessel formation and cell proliferation. More recently, apelin has been described as an adipocyte-secreted factor (adipokine), up-regulated in obesity. By acting as circulating hormone or paracrine factor, adipokines are involved in physiological regulations (fat depot development, energy storage, metabolism or eating behavior) or in the promotion of obesity-associated disorders (type 2 diabetes and cardiovascular dysfunctions). In this regard, expression of apelin gene in adipose tissue is increased by insulin and TNFalpha. This review will consider the main roles of apelin in physiopathology with particular attention on its role in energy balance regulation and in obesity-associated disorders.
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PMID:Expanding role for the apelin/APJ system in physiopathology. 1845 11

Adiponectin is an anti-diabetic and anti-atherogenic adipokine that serves as a major determinant of insulin sensitivity. Thiazolidine derivatives increase circulating adiponectin, particularly the high molecular weight isoform, which has been shown to well correlate with amelioration of insulin resistance by thiazolidines in diabetic patients. alpha-glucosidase inhibitors are another class of anti-diabetic agents that specifically reduce postprandial blood glucose elevations, but its effect on adiponectin is largely unknown. In the present study we investigated effect of an alpha-glucosidase inhibitor, acarbose, together with pioglitazone, the only thiazolidine derivative available in Japan, on serum concentrations of adiponectin. Seventeen patients with type 2 diabetes were treated with acarbose and sixteen with pioglitazone for three months. Treatment with acarbose and pioglitazone decreased HbA1c values by 0.49% and 0.63%, respectively. Pioglitazone, as expected, increased serum levels of total adiponectin by 2.1 fold and its high molecular weight isoform by 3.6 fold. We found that acarbose also caused a small but significant increase in serum concentrations of total adiponectin. However, in contrast to pioglitazone, no appreciable changes were observed in the levels of high molecular weight adiponectin. In conclusion, acarbose increases serum concentrations of total adiponectin without preference of the high molecular weight isoform in type 2 diabetic patients. Clinical relevance of the increased adiponectin to the acarbose effects remains to be elucidated.
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PMID:Acarbose treatment increases serum total adiponectin levels in patients with type 2 diabetes. 1848 May 56

Adipose tissue is increasingly recognized as a metabolically active endocrine organ with multiple functions beyond its lipid storage capability. Various constituents of the tissue, such as mature adipocytes and stromal vascular cells, have distinct functions. For example, they express and secrete different kinds of bioactive molecules collectively called adipokines. Altered adipokine secretion patterns characterize obesity and insulin resistance, which are major risk factors for type 2 diabetes mellitus. The contribution of dysregulated adipokine expression to these diseases may be assembled from transcriptomic profiles of the tissue and/or its cellular constituents. The gene expression profiles may also complement genetic approaches to identify disease susceptibility genes. Here, we describe an application of gene expression profiling using DNA microarrays to study human adipose tissue, adipocytes, and stromal vascular cells.
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PMID:Application of DNA microarray to the study of human adipose tissue/cells. 1851 59

The insulin-sensitizing adipokine, adiponectin, acts through 2 receptors, AdipoR1 and AdipoR2. A decreased expression of these receptors could contribute to insulin resistance and diabetes. We determined if the expression of adiponectin receptors is decreased in an experimental model, the Zucker diabetic rat (ZDF), and if a peroxisome proliferator-activated receptor alpha agonist, fenofibrate, and metformin could increase these expressions. The ZDF and control (L) rats were studied at 7, 14, and 21 weeks. After initial study at 7 weeks, ZDF received no treatment (n = 10), metformin (n = 10), or fenofibrate (n = 10) until final studies at 14 or 21 weeks. The L rats received no treatment. AdipoR1 and R2 expressions were measured in liver, muscle, and white adipose tissue (WAT). As expected, ZDF rats were insulin resistant at 7 weeks, had type 2 diabetes mellitus at 14 weeks, and had diabetes with insulin deficiency at 21 weeks. Compared with L rats, AdipoRs messenger RNA was decreased only in the WAT (P < .05) of 7-week-old ZDF rats, but was unchanged in muscle and increased in liver. Metformin and fenofibrate decreased plasma triacylglycerols (P < .01) as expected. The only effect of fenofibrate on AdipoRs was a moderate increase (P < .01) of both receptors' messenger RNA in liver. Metformin increased AdipoR1 and R2 expression in muscle (P < .01) and AdipoR1 (P < .01) in WAT. These results do not support an important role for decreased AdipoRs expression in the development of insulin resistance and diabetes. Parts of the actions of fenofibrate and of metformin could be mediated by a stimulation of the expression of these receptors in liver and in insulin-sensitive, glucose-utilizing tissues (muscle, WAT), respectively.
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PMID:Adiponectin receptors: expression in Zucker diabetic rats and effects of fenofibrate and metformin. 1855 36

Adiponectin is an adipokine, which is expressed in adipose tissue and is thought to play an important role in glucose metabolism. Hypoadiponectinemia can cause reduction of fatty acid oxidation, decreased glucose uptake in skeletal muscle cells, and increased gluconeogenesis in hepatic cells. The level of plasma glucose can be increased. On the other hand, the decrease of fatty acid oxidation increases the level of free fatty acid (FFA), which increases the insulin resistance, and then decreases the glucose uptake, which ultimately causes increased plasma glucose and type 2 diabetes (T2D). This review describes the process from hypoadiponectinemia to T2D and the genesis of hypoadiponectinemia at a molecular level.
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PMID:Adiponectin and its association with insulin resistance and type 2 diabetes. 1857 Nov 19

The metabolic syndrome is a constellation of metabolic risk factors and physical conditions that are accompanied by an enhanced propensity toward the development of type 2 diabetes, atherosclerosis, and cardiovascular disease. It presents a combination of atherosclerosis risk including atherogenic dyslipidemia, hypertension, elevated plasma glucose, hypercoagulability, and a proinflammatory state. The 2 major underlying risk factors for the metabolic syndrome are obesity and insulin resistance. Exacerbating factors are physical inactivity, advancing age, and endocrine and genetic factors. Associated hyperinsulinemia, hyperglycemia, and elevated adipokine levels (adipose cytokines) lead to vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease. In this 2-part series, the authors present an up-to-date and detailed systematic review of the literature on this important topic.
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PMID:The metabolic syndrome and cardiovascular disease: Part I. 1860 51

Vaspin has recently been identified as novel adipokine with high expression in adipose tissue of obese and type 2 diabetic subjects and with potentially insulin-sensitising properties. However, the impact of vaspin gene variants on the risk of type 2 diabetes mellitus (T2DM) has not been determined yet. Therefore, the aim of our study was to investigate the association of vaspin single nucleotide polymorphisms (SNPs) with T2DM and obesity. We analysed the association between 25 vaspin SNPs and T2DM in initially healthy 35-84 year-old individuals of the population-based, cross-sectional German KORA F3 study and assessed the association with measures of obesity. Genotyping was carried out with matrix-assisted laser desorption/ionisation-time of flight mass spectrometry of allele-dependent primer extension products and associations with T2DM and obesity were analysed by logistic regression analysis. Our results demonstrate a significant association of vaspin SNP rs2236242 with T2DM in the KORA F3 study with the AA genotype bearing an increased risk (adjusted OR 2.35 [1.59; 3.46] versus AT/TT). This association appears to be independent of obesity. Our finding corroborates previous studies that suggested a link between the novel adipokine vaspin and glucose metabolism.
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PMID:Vaspin (SERPINA12) genotypes and risk of type 2 diabetes: Results from the MONICA/KORA studies. 1872 71

Inflammation is a key pathological process in the progression of atherosclerosis and type 2 diabetes. 12/15-lipoxygenase (12-LO), an enzyme involved in fatty acid metabolism, may contribute to inflammatory damage triggered by stressors such as obesity and insulin resistance. We hypothesized that mice lacking 12-LO are protected against inflammatory-mediated damage associated with a "western" diet. To test this hypothesis, age-matched male 12-LO knockout (12-LOKO) and wild-type C57BL/6 (B6) mice were fed either a standard chow or western diet and assessed for several inflammatory markers. Western-fed B6 mice showed expected reductions in glucose and insulin tolerance compared with chow-fed mice. In contrast, western-fed 12-LOKO mice maintained glucose and insulin tolerance similar to chow-fed mice. Circulating proinflammatory cytokines, tumor necrosis factor-alpha and interleukin-6, were increased in western B6 mice but not 12-LOKO mice, whereas the reported protective adipokine, adiponectin, was decreased only in western B6 mice. 12-LO activity was significantly elevated by western diet in islets from B6 mice. Islets from 12-LOKO mice did not show western-diet-induced islet hyperplasia or increases in caspase-3 apoptotic staining observed in western-fed B6 mice. Islets from 12-LOKO mice were also protected from reduced glucose-stimulated insulin secretion observed in islets from western-fed B6 mice. In visceral fat, macrophage numbers and monocyte chemoattractant protein-1 expression were elevated in western B6 mice but not 12-LOKO mice. These data suggest that 12-LO activation plays a role in western-diet-induced damage in visceral fat and islets. Inhibiting 12-LO may provide a new therapeutic approach to prevent inflammation-mediated metabolic consequences of excess fat intake.
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PMID:12-Lipoxygenase-knockout mice are resistant to inflammatory effects of obesity induced by Western diet. 1878 Jul 76

Exendin 4 (Ex4) is a glucagon-like peptide-1 receptor (GLP- 1R) agonist which is available as a short-acting injectable treatment for type 2 diabetes. Our aim was to characterize the long-term effects of elevated steady-state levels of Ex4 provided by in vivo gene therapy. We constructed a helper-dependent adenoviral (HDAd) vector for long-term expression of Ex4 in vivo. A high-fat diet (HFD)-induced obesity (DIO) mouse model was chosen to approximate the metabolic derangements seen in obese patients. Mice were treated with a single injection of HDAd-Ex4 and were monitored for 15 weeks. Both hepatic Ex4 RNA and plasma Ex4 were detectable at the end of the study. HDAd-Ex4 treatment improved glucose homeostasis without increasing insulin levels. However, there was evidence of enhanced insulin action and decreased gluconeogenic enzyme expression. HDAd-Ex4 caused decreased weight gain without detectable changes in food intake, in part, due to increases in energy expenditure (EE). HDAd-Ex4 DIO mice also had reduced hepatic fat and an improved adipokine profile. In the liver, there was decreased expression of genes that were involved in de novo fatty acid synthesis. These observations are important in considering the development of longer acting GLP-1R agonists for the treatment of type 2 diabetes.
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PMID:Gene therapy for diabetes: metabolic effects of helper-dependent adenoviral exendin 4 expression in a diet-induced obesity mouse model. 1878 Nov 41


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