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)

Resistin is an adipokine whose physiologic role in obesity, type II diabetes mellitus, and inflammatory diseases has been a subject of debate because while it is expressed in adipocytes and adipose tissue in mouse, it is expressed in leukocytes, such as macrophages, in human. In the present study, we attempt to define the effect of resistin on human dendritic cells (DCs) derived from CD14(+) monocytes. When DCs were stimulated with lipoteichoic acid (LTA) and treated with various concentrations of resistin, antigen-uptake process and the endocytic capacity of DCs were decreased. It is intriguing that resistin attenuated cytokine production in LTA-primed DCs. Consequently, T cell activity was reduced when lymphocytes were mixed with Staphylococcus aureus-primed autologous DCs treated with resistin compared to S. aureus-primed DCs without resistin. Our results suggest that resistin interferes with the efficacy of immune responses activated by Gram-positive bacterial infection in human DCs.
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PMID:Immunomodulatory effect of resistin in human dendritic cells stimulated with lipoteichoic acid from Staphylococcus aureus. 1880 95

Beta-cell apoptosis induced by adipokines may result in beta-cell dysfunction in type 2 diabetes. Resistin, an adipokine-linked obesity with type 2 diabetes, impairs glucose-stimulated insulin secretion (GSIS) in beta-cells. Presently, the effects of resistin on rat insulinoma cells RINm5F were examined. Treatment of RINm5F with resistin induced cell damage. Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) protected resistin-mediated cytotoxicity in RINm5F. Incubation with resistin up-regulated caspase-3 activity and induced the formation of a DNA ladder. TIMP-1 attenuated these effects. The molecular mechanism of TIMP-1 inhibition of resistin-mediated cytotoxicity appeared to involve Akt phosphorylation and activation of IkB-alpha phosphorylation. Resistin treatment suppressed Akt phosphorylation and activated IkB-alpha phosphorylation, which could be attenuated by TIMP-1. We conclude that resistin can induce beta-cell apoptosis and that resistin-related beta-cell apoptosis can be prevented by TIMP-1.
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PMID:Resistin induces rat insulinoma cell RINm5F apoptosis. 1883 35

Adiponectin, an adipokine secreted by the white adipose tissue, plays an important role in regulating glucose and lipid metabolism and controlling energy homeostasis in insulin-sensitive tissues. A decrease in the circulating level of adiponectin has been linked to insulin resistance, type 2 diabetes, atherosclerosis, and metabolic syndrome. Adiponectin exerts its effects through two membrane receptors, AdipoR1 and AdipoR2. APPL1 is the first identified protein that interacts directly with adiponectin receptors. APPL1 is an adaptor protein with multiple functional domains, the Bin1/amphiphysin/rvs167, pleckstrin homology, and phosphotyrosine binding domains. The PTB domain of APPL1 interacts directly with the intracellular region of adiponectin receptors. Through this interaction, APPL1 mediates adiponectin signaling and its effects on metabolism. APPL1 also functions in insulin-signaling pathway and is an important mediator of adiponectin-dependent insulin sensitization in skeletal muscle. Adiponectin signaling through APPL1 is necessary to exert its anti-inflammatory and cytoprotective effects on endothelial cells. APPL1 also acts as a mediator of other signaling pathways by interacting directly with membrane receptors or signaling proteins, thereby playing critical roles in cell proliferation, apoptosis, cell survival, endosomal trafficking, and chromatin remodeling. This review focuses mainly on our current understanding of adiponectin signaling in various tissues, the role of APPL1 in mediating adiponectin signaling, and also its role in the cross-talk between adiponectin/insulin-signaling pathways.
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PMID:APPL1: role in adiponectin signaling and beyond. 1885 21

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

Obstructive sleep apnea syndrome (OSAS) is related to the increased prevalence of cardiovascular disease and metabolic syndrome (MS). A novel adipokine, retinol binding protein-4 (RBP4), was reported to be associated with insulin resistance and the prevalence of type 2 diabetes. To examine whether plasma RBP4 is associated with insulin resistance and MS development in OSAS, we measured plasma RBP4 levels in 181 Japanese men (24 healthy controls and 40 mild, 64 moderate, and 53 severe OSAS) of whom 26 had mild glucose intolerance with HbA1c < or = 6.0%. After a full polysomnography, blood was collected between 06:00 and 07:00 AM. Plasma RBP4 levels in moderate/severe OSAS patients were higher than in control subjects. Plasma RBP4 was not correlated with apnea variables, HOMA-IR, or blood pressure. However, it was positively correlated with visceral fat areas and plasma triglyceride levels. The prevalence of MS was higher in severe OSAS patients than in mild/moderate OSAS and control subjects. Plasma RBP4 was higher in OSAS patients with MS than in those without MS. This study indicates that plasma RBP4 is associated with dyslipidemia, but not with insulin resistance, glucose intolerance, or hypertension in patients with OSAS. Visceral obesity may play key roles in increasing the plasma RBP4 level and MS development in OSAS.
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PMID:Visceral obesity is associated with the metabolic syndrome and elevated plasma retinol binding protein-4 level in obstructive sleep apnea syndrome. 1900 25

The correlation of body mass index (BMI) with both adiposity and risk for type 2 diabetes mellitus (DM) is positive. An elevated BMI is also associated with increased mortality from cardiovascular disease (CVD). However, for any given BMI measurement, some persons are at risk for type 2 DM and CVD, while others are not. This disparity of risk may relate to differences in age, fitness, and body composition, including body fat. Obesity- excess body fat- is associated with insulin resistance. Abdominal obesity, in particular, places people at higher risk for developing insulin resistance and, consequently, is associated with an increased risk for type 2 DM and CVD. The association between obesity and insulin resistance is largely due to changes in the function of adipose tissue, specifically, increased release of free fatty acids and abnormalities in adipokine secretion. The properties of visceral adipose tissue may cause these dysfunctions to become magnified. Weight loss has the potential to improve insulin sensitivity through alterations in adipose tissue function.
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PMID:Obesity, abdominal obesity, and insulin resistance. 1904 37

In view of the central role of preadipocyte factor-1, adiponectin and leptin in white adipose tissue function, the aim of the present study was to analyze the mRNA expression of these proteins and of the inflammatory markers interleukin-6 and tumor necrosis factor-alpha in visceral and subcutaneous fat pads of rats with different metabolic disorders. We demonstrated highly divergent expression of preadipocyte factor-1, upregulated expression of adiponectin, interleukin-6 and TNF-alpha mRNA in adipose tissues of the diabetic Goto Kakizaki rat compared to the obese Zucker rat. This was correlated to an increased number of large adipocytes and serum levels of adiponectin. Furthermore, in all four strains studied (as above plus Wistar Furth and Zucker Lean), significant heterogeneity was evident in adipokine expression within specific adipose tissues previously defined as belonging to the visceral or subcutaneous fat depots. These results suggest that significantly increased levels of inflammation and redistribution of adipocyte size are mechanisms contributing to the development of type 2 diabetes in the GK rat.
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PMID:Pref-1 and adipokine expression in adipose tissues of GK and Zucker rats. 1908 46

Inhibitors of the angiotensin-converting enzyme (ACE) decrease angiotensin II production and activate an intracellular signaling cascade that affects gene expression in endothelial cells. Because ACE inhibitors have been reported to delay the onset of type 2 diabetes, we determined ACE signaling-modulated gene expression in endothelial cells and adipocytes. Using differential gene expression analysis, several genes were identified that were 3-fold up- or down-regulated by ramiprilat in cells expressing wild-type ACE versus cells expressing a signaling-dead ACE mutant. One up-regulated gene was the cellular retinol-binding protein 1 (CRBP1). In adipocytes, the overexpression of CRBP1 enhanced (4- to 5-fold) the activity of promoters containing response elements for retinol-dependent nuclear receptors [retinoic acid receptor (RAR) and retinoid X receptor (RXR)] or peroxisome proliferator-activated receptors (PPAR). CRBP1 overexpression also enhanced the promoter activity (by 470 +/- 40%) and expression/release of the anti-inflammatory and antiatherogenic adipokine adiponectin (cellular adiponectin by 196 +/- 24%, soluble adiponectin by 228 +/- 74%). Significantly increased adiponectin secretion was also observed after ACE inhibitor treatment of human preadipocytes, an effect prevented by small interfering RNA against CRBP1. Furthermore, in ob/ob mice, ramipril markedly potentiated both the basal (approximately 2-fold) and rosiglitazonestimulated circulating levels of adiponectin. In patients with coronary artery disease or type 2 diabetes, ACE inhibition also significantly increased plasma adiponectin levels (1.6- or 2.1-fold, respectively). In summary, ACE inhibitors affect adipocyte homeostasis via CRBP1 through the activation of RAR/RXR-PPAR signaling and up-regulation of adiponectin. The latter may contribute to the beneficial effects of ACE inhibitors on the development of type 2 diabetes in patients with an activated renin-angiotensin system.
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PMID:Angiotensin-converting enzyme (ACE) inhibitors modulate cellular retinol-binding protein 1 and adiponectin expression in adipocytes via the ACE-dependent signaling cascade. 1911 89

Adiponectin and adiponectin receptors (AdipoRs) have been found to play significant roles in the etiology of obesity-related chronic disease. Their discovery has been a long and complicated path, with many challenges. Developing methods to unravel the molecular secrets has been an informative process in itself. However, with both functional and genetic studies confirming adiponectin as a therapeutic target adipokine, many roles and interactions with certain other biomolecules have been clearly defined. We have found that decreased high molecular weight (HMW) adiponectin plays a crucial and causal role in obesity-linked insulin resistance and metabolic syndrome; that AdipoR1 and AdipoR2 serve as the major AdipoRs in vivo; and that AdipoR1 activates the AMP kinase (AMPK) pathway and AdipoR2, the peroxisome proliferator-activated receptor alpha (PPARalpha) pathway in the liver, to increase insulin sensitivity and decrease inflammation. Further conclusions are that decreased adiponectin action and increased monocyte chemoattractant protein-1 (MCP-1) form a vicious adipokine network causing obesity-linked insulin resistance and metabolic syndrome; PPARgamma upregulates HMW adiponectin and PPARalpha upregulates AdipoRs; that dietary osmotin can serve as a naturally occurring adiponectin receptor agonist; and finally, that under starvation conditions, MMW adiponectin activates AMPK in hypothalamus, and promotes food intake, and at the same time HMW adiponectin activates AMPK in peripheral tissues, such as skeletal muscle, and stimulates fatty-acids combustion. Importantly, under pathophysiological conditions, such as obesity and diabetes, only HMW adiponectin was decreased; therefore, strategies to increase only HMW adiponectin may be a logical approach to provide a novel treatment modality for obesity-linked diseases, such as insulin resistance and type 2 diabetes. It is hoped that these data will be helpful in developing treatments to counteract the destructive, expensive and painful effects of obesity.
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PMID:Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases. 1913 82

We aimed at determining which circulating forms of the adipokine adiponectin that increases lipid oxidation in liver and skeletal muscle are related to ectopic fat in these depots in humans. Plasma total-, high-molecular weight (HMW)-, middle-molecular weight (MMW)-, and low-molecular weight (LMW) adiponectin were quantified by an enzyme-linked immunosorbent assay. Their relationships with liver- and intramyocellular fat, measured using (1)H magnetic resonance spectroscopy, were investigated in 54 whites without type 2 diabetes. Liver fat, adjusted for gender, age, and total body fat, was associated only with HMW adiponectin (r = -0.35, P = 0.012), but not with total-, MMW-, or LMW adiponectin. In addition, subjects with fatty liver (liver fat > or =5.56%, n = 15) had significantly lower HMW- (P = 0.04), but not total-, MMW-, or LMW adiponectin levels, compared to controls (n = 39). Similarly, intramyocellular fat correlated only with HMW (r = -0.32, P = 0.039), but not with the other circulating forms of adiponectin. These data indicate that, among circulating forms of adiponectin, HMW is strongly related to ectopic fat, thus possibly representing the form of adiponectin regulating lipid oxidation in liver and skeletal muscle.
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PMID:Adiponectin oligomers and ectopic fat in liver and skeletal muscle in humans. 1916 22


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