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)

Visfatin was recently identified as a novel adipokine highly enriched in visceral adipose tissue and suggested to play a role in the pathophysiology of obesity and type 2 diabetes mellitus. However, the biological role of visfatin remains elusive since subsequent studies failed to repeat some of the original findings. We report here the cloning of six porcine visfatin transcript variants, resulting from alternate polyadenylation or alternate splicing of exons. It is further demonstrated that the porcine visfatin gene and protein expression measured in fat tissues correlate negatively with subcutaneous (s.c.), visceral and total body fat tissue weights. Moreover, there was no correlation between visfatin mRNA or protein levels and fasting glucose or insulin. No correlation could be found between circulating visfatin and any of the carcass and metabolic parameters. Our results also demonstrate that the tumor necrosis factor (TNF)alpha increases porcine visfatin gene expression in stromal-vascular (SV) cell cultures, thus suggesting an intermediary role for TNFalpha in visfatin response. In conclusion, our results demonstrate that the porcine visfatin gene cannot be considered as a marker of fat accumulation since the highest visfatin expression levels were associated with the leaner animals.
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PMID:Visfatin expression is not associated with adipose tissue abundance in the porcine model. 1834 25

Visfatin is an independent association factor for type 2 diabetes mellitus (T2DM). In order to evaluate the plasma visfatin levels and investigate whether plasma visfatin concentrations are altered by intensive glycemic control in patients with diabetes, we determined plasma visfatin concentrations and metabolic parameters in 53 newly diagnosed type 2 diabetic patients and 35 healthy controls. Visfatin levels were also investigated before and after intensive glycemic control for three months in subgroup of patients with T2DM. Plasma visfatin levels were significantly elevated in diabetic patients compared with healthy controls (p<0.001). Circulating visfatin concentration was associated with fasting plasma glucose (FPG), 2-hour OGTT plasma glucose (2hPG), HOMA-beta indexes (r=0.338, p=0.001; r=0.340, p=0.002; r=-0.296, p=0.006, respectively), but not with insulin sensitivity (HOMA-IR) or other metabolic or anthropometric parameters in all subjects. In addition, visfatin levels were also correlated with HbA1c levels in diabetic patients. Furthermore, visfatin concentrations reduced from 25.0+/-6.5 ng/ml at baseline to 20.3+/-4.7 ng/ml (p<0.01) after 3 months of intensive glycemic control, while HbA1c levels decreased from 9.0+/-1.8% to 6.2+/-0.7% (p<0.01). We conclude that the change of visfatin concentration may be a compensatory mechanism to ameliorate insulin deficiency due to pancreatic beta-cell dysfunction.
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PMID:Intensive glycemic control lowers plasma visfatin levels in patients with type 2 diabetes. 1868 25

Visfatin is a newly discovered adipocyte hormone with a direct relationship between plasma visfatin level and type 2 diabetes mellitus. Visfatin binds to the insulin receptor at a site distinct from that of insulin and causes hypoglycaemia by reducing glucose release from liver cells and stimulating glucose utilization in adipocytes and myocytes. Visfatin is upregulated by hypoxia, inflammation and hyperglycaemia and downregulated by insulin, somatostatin and statins. This hormone is found in the cytoplasm as well as the nucleus of cells and has been identified in many tissues and organs including the brain, kidney, lung, spleen and testis but preferentially expressed in visceral adipose tissue and upregulated in some animal models of obesity. Visceral adipose tissue is regarded to be more pernicious than subcutaneous adipose tissue. Visfatin is an endocrine, autocrine as well as paracrine peptide with many functions including enhancement of cell proliferation, biosynthesis of nicotinamide mono- and dinucleotide and hypoglycaemic effect. Visfatin, also known as a pre-B cell colony-enhancing factor, consists of 491 amino acids (aa) in human, chimpanzee, cattle, pig, rat and mouse, 490 aa in rhesus monkey, 285 aa in sheep, 587 in opossum and 588 aa in canines. Visfatin gene is well preserved during evolution. For example, the canine visfatin protein sequence is 96% and 94% identical to human and rodent visfatin, respectively. Since evidence of a direct link between visfatin genotype and human type 2 diabetes mellitus is still weak, more molecular, physiological and clinical studies are needed to determine the role of visfatin in the etiology and pathogenesis of type 2 diabetes mellitus.
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PMID:Visfatin: structure, function and relation to diabetes mellitus and other dysfunctions. 1869 Oct 43

Visfatin is a recently described new adipokine that is considered to bind to the insulin receptor and induce insulin action via signal transduction pathways distinct from those of insulin. This study investigated whether circulating plasma visfatin levels may be influenced by PPARy activation, as shown for adiponectin and other adipokines. Samples from a prospective single-blinded placebo-controlled three-month intervention study with rosiglitazone were retrospectively analysed. The samples were derived from 39 patients with type 2 diabetes mellitus suffering from coronary artery disease as confirmed by angiography (rosiglitazone arm: 18 men, 1 woman, age (mean +/- STD): 65 +/- 9 years, disease duration: 4.8 +/- 4.0 years, HbA1c: 7.3 +/- 1.3%; Placebo: 19 men, 1 woman, age: 64 +/- 10 years, disease duration: 5.1 +/- 6.5 years, HbA1c: 7.5 +/- 1.5%). Laboratory measurements for lipids, adiponectin, and visfatin were performed with validated tests. The baseline values were comparable for all observation markers. After three months, a significant increase in the adiponectin concentrations could be observed only in the rosiglitazone group (from: 6.9 +/- 0.9 mg/l to 16.5 +/- 1.5 mg/l, (p < 0.001) vs placebo: 7.8 +/- 6.3 mg/l to 8.0 +/- 0.8 mg/l, (n.s.), p < 0.001 between the groups at endpoint). No changes were seen in both treatment arms for the other observation parameters. In particular, no influence of rosiglitazone was seen on the visfatin concentrations (25.9 +/- 2.3 ng/ml to 25.8 +/- 1.9 ng/ml; Placbo: 26.9 +/- 5.4 ng/ml to 27.2 +/- 4.9 ng/ml, n.s.). Our investigation demonstrates that rosiglitazone has different effects on circulating concentrations of adiponectin and visfatin. Visfatin secretion is not regulated by PPARgamma and further research is required to investigate its role in insulin resistance.
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PMID:Impact of rosiglitazone on visfatin and adiponectin plasma concentrations in patients with type 2 diabetes and coronary artery disease. 1894 91

Nicotinamide phosphoribosyltransferase (Nampt) converts nicotinamide to nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD) intermediate. Previously identified as a cytokine pre-B-cell colony-enhancing factor and controversially claimed as an insulin-mimetic hormone visfatin, Nampt has recently drawn much attention in several fields, including NAD biology, metabolism and inflammation. As a NAD biosynthetic enzyme, Nampt regulates the activity of NAD-consuming enzymes such as sirtuins and influences a variety of metabolic and stress responses. Nampt also plays an important part in regulating insulin secretion in pancreatic beta-cells. Nampt seems to have another function as an immunomodulatory cytokine and, therefore, has a role in inflammation. This review summarizes these various functional aspects of Nampt and discusses its potential roles in diseases, including type 2 diabetes and cancer.
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PMID:Nampt: linking NAD biology, metabolism and cancer. 1910 34

Both genetic and environmental factors contribute to the pathogenesis of type 2 diabetes, and it is critical to understand the interplay between these factors in the regulation of insulin secretion and insulin sensitivity to develop effective therapeutic interventions for type 2 diabetes. For the past several years, studies on the mammalian NAD-dependent protein deacetylase SIRT1 and systemic NAD biosynthesis mediated by nicotinamide phosphoribosyltransferase (NAMPT) have demonstrated that these two regulatory components together play a critical role in the regulation of glucose homeostasis, particularly in the regulation of glucose-stimulated insulin secretion in pancreatic beta cells. These components also contribute to the age-associated decline in beta cell function, which has been suggested to be one of the major contributing factors to the pathogenesis of type 2 diabetes. In this review article, the roles of SIRT1 and NAMPT-mediated systemic NAD biosynthesis in glucose homeostasis and the pathophysiology of type 2 diabetes will be summarized, and their potential as effective targets for the treatment and prevention of type 2 diabetes will be discussed.
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PMID:Therapeutic potential of SIRT1 and NAMPT-mediated NAD biosynthesis in type 2 diabetes. 1927 50

Visfatin was recently reported as a novel adipokine encoded by the NAMPT (PBEF1) gene. This study was aimed at investigation of the possibility that single-nucleotide polymorphisms (SNPs) in the visfatin gene are associated with either obesity or type 2 diabetes (T2D). A set of eight "tag-SNPs" were selected and ABI SNPlex assays designed for genotyping purposes. A total of 1,709 severely obese subjects were typed (896 class III obese adults and 813 children) together with 2,367 T2D individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818 from a general population sample. One rare SNP, rs10487818, located in intron 4 of NAMPT was associated with severe obesity, with a minor allele frequency of 1.6% in controls, 0.4% in the class III obese adults and, remarkably, 0% in the severely obese children. A highly significant association was observed for the presence or absence of the rare allele, i.e., (A,A) vs. (A,T + T,T) genotypes, in children (P = 6 x 10(-9)) and in adults (P = 8 x 10(-5)). No other significant (P < 0.05) association was observed with obesity or T2D for this or any other SNP. No association with BMI or waist-to-hip ratio was observed in a general population sample (n = 5,212). This is one of the first rare SNPs shown to be protective against a common polygenic disease and provides further evidence that rare alleles of strong effect can contribute to complex diseases such as severe obesity.
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PMID:A rare variant in the visfatin gene (NAMPT/PBEF1) is associated with protection from obesity. 1930 Apr 29

Adipose tissue cells express and secrete numerous proteins influencing the signal transduction pathways of insulin receptor by auto-, para- and endocrine manner. Several cytokines, tumor necrosis factor-alpha and its soluble receptor forms, sTNFR1 and sTNFR2, resistin, retinol-binding protein 4, plasminogen activator inhibitor, lipocain 1 inhibit the signalization of insulin receptor causing insulin resistance in target tissues, mainly in adipose, liver and muscle, brain, endothelial as well as in pancreatic beta-cells. However, many other proteins produced by the fat tissue, such as adiponectin, visfatin, vaspin, apelin, omentin and chemerin enhance the signal transmission of the receptor. Recently discovered common mechanisms leading to insulin and cytokine resistance in obesity and type 2 diabetes mellitus, e.g. protein family of suppressor of cytokine signaling (SOCS) are also discussed.
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PMID:[Molecular mechanisms and correlations of insulin resistance, obesity, and type 2 diabetes mellitus]. 1972 6

White adipose tissue is an endocrine organ producing numerous proteins known as adipokines, which include leptin, adiponectin, resistin, visfatin, and other factors, which are involved in most metabolic disorders. In obesity, plasma leptin concentrations are high due to leptin resistance that may result from the attenuation of leptin signaling in the hypothalamus. Leptin acts to inhibit appetite, stimulate thermogenesis, enhance fatty acid oxidation, decrease glucose, and reduce body weight, and fat. A reduced adiponectin level has been associated with insulin resistance, dyslipidemia, and atherosclerosis, and its low level is a predictor of later development of type 2 diabetes. Resistin expression is low in adipose tissue and high in bone marrow and lungs, its role in glucose homeostasis remains controversial, it has been associated with insulin resistance and obesity. Visfatin is a secretory protein highly enriched in visceral adipocytes, liver, muscle, and lymphocytes. An increase of visfatin levels in obesity was related to preservation of insulin sensitivity, it enhances glucose uptake by adipocytes and inhibits hepatocyte glucose release, it induces tyrosine phosphorylation, and interacts with insulin receptors. Many studies are still being conducted to highlight the role of adipokines in metabolic disorders.
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PMID:Adipokines and etiopathology of metabolic disorders. 1975 Feb 55

Diabetes is an important health problem since the incidence of diabetes is continuously increasing. Early diagnosis is important as type 2 diabetes begins long before we diagnose it, leading to a complicated course of the disease. In order to prevent delay in the diagnosis of type 2 diabetes, novel predictors and pathways for type 2 diabetes are mounting. Diabetic complications are common cause of morbidity and mortality among subjects with diabetes. In the pathogenesis of diabetic complications some factors other than chronic hyperglycemia may be involved. Adipocytokines play important roles in the pathogenesis of diabetes mellitus, insulin resistance, and associated metabolic conditions such as hypertension and dyslipidemia. The investigations on the role of adipocytokines in developing diabetes and its complications have been made. In this review, we discussed the implications of adipocytokines in predicting diabetes and diabetic complications, with particular attention on the roles of adiponectin, leptin, visfatin, and vaspin.
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PMID:Role of adipocytokines in predicting the development of diabetes and its late complications. 1977 67


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