Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80098 (monocyte chemoattractant protein)
 1,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis has highly important chronic inflammatory aspects. We investigated anti-inflammatory effects upon initiating insulin therapy by measuring serum high-sensitivity C-reactive protein (hsCRP) and plasma fibrinogen and serum monocyte chemoattractant protein (MCP)-1in patients with poorly controlled type 2 diabetes. In 18 inpatients with type 2 diabetes, we measured serum hsCRP, plasma fibrinogen, serum MCP-1, body weight (BW), girth, and fasting plasma glucose (FPG) before and 2 weeks (14.0 +/- 2.5 days) after initiation of insulin therapy. Daily insulin doses (in units) were approximately 0.2 x BW (in kilograms). Various changes (ratio) were calculated as the ratio of the value during treatment to the pretreatment value. Significant decreases occurred for log(10) hsCRP and FPG (-0.025 +/- 0.557 mg/L, 215 +/- 64.3 mg/dL v -0.213 +/- 0.571 mg/L, 129.8 +/- 32.1 mg/dL; P =.0121, and P =.00002, respectively). This was particularly true for log(10) hsCRP in patients whose BW was unchanged or increased between measurement (P =.0050). There were no significant differences between pretreatment and treatment values for fibrinogen and MCP-1. However, MCP-1 decreased significantly in the group with high-value in the first time point (MCP-1 > 250 pg/mL, n = 9; P =.0224) compared with the low-value group (MCP-1 < 250 pg/mL, n = 9; P =.3164). No significant correlation was found between hsCRP ratio and fibrinogen ratio, MCP-1 ratio, BW ratio, waist girth ratio, or FPG ratio. In conclusion, newly initiated insulin therapy in patients with poorly controlled type 2 diabetes decreased serum hsCRP. The decrease in hsCRP may have resulted largely from anti-inflammatory effects of insulin.
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PMID:Initiation of insulin therapy reduces serum concentrations of high-sensitivity C-reactive protein in patients with type 2 diabetes. 1516 14

Diabetes is associated with an enhanced collagen-mediated platelet activation that contributes significantly to thromboischemic complications. In this study, the platelet collagen receptor glycoprotein VI (GPVI) was studied in 385 patients with type 2 diabetes. Surface expression of the platelet Fc receptor that forms a functional complex with GPVI was significantly increased in patients with diabetes compared with those without diabetes (P = 0.02). Fc receptor expression correlated with GPVI expression and was found to be independently associated with diabetes (r = 0.529, P < 0.001). Stimulation of GPVI through a specific anti-GPVI monoclonal antibody significantly enhanced surface expression of CD40L (P = 0.006). Because CD40L is a potent platelet-derived cytokine that is involved in thrombosis and atherosclerosis, we evaluated the effect of GPVI-mediated release of CD40L on activation of endothelial cells. Coincubation of GPVI-stimulated platelets resulted in substantial enhanced endothelial surface expression of CD62P, alphavbeta3, and intercellular adhesion molecule 1 (P < 0.05) and secretion of monocyte chemoattractant protein 1 of cultured human umbilical vein endothelial cells (P < 0.01). These results suggest that the function of collagen receptor GPVI is altered in type 2 diabetes and may play an important role in atherothrombotic complications. Inhibition of GPVI may be a promising pharmacological target in the treatment of high-risk diabetic patients.
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PMID:Surface expression of collagen receptor Fc receptor-gamma/glycoprotein VI is enhanced on platelets in type 2 diabetes and mediates release of CD40 ligand and activation of endothelial cells. 1527 94

The effect of low-dose atorvastatin on various biomarkers was investigated in patients with type 2 diabetes complicated by hyperlipidemia. At 0 and 12 weeks in both the atorvastatin group (10 mg/d; n=17) and the no-drug group (n=10), high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein (MCP)-1, plasminogen activator inhibitor (PAI)-1, and fibrinogen were measured. At baseline, the entire group of diabetic patients (n=27) had significantly higher values of hsCRP and fibrinogen compared with those in age-matched healthy subjects (n=29): 0.801 (0.306, 1.760) vs 0.282 (0.143, 0.6505) mg/L, P=.0042; 329.1+/-55.0 vs 212.4+/-35.9 mg/dL, P<.0001, respectively. High-sensitivity C-reactive protein decreased significantly with atorvastatin treatment, from 0.801 (0.243, 1.865) to 0.308 (0.200, 0.804) mg/L (P=.0191). Although MCP-1, PAI-1, and fibrinogen did not decrease in the atorvastatin patients overall, the decrease of MCP-1 was significant in women (n=10; from 241.9+/-45.8 to 215.4+/-49.5 pg/mL, P=.0332). No correlation was found between changes in the serum lipid concentrations and changes in hsCRP, MCP-1, PAI-1, or fibrinogen in either the atorvastatin or the no-drug group. In conclusion, low-dose atorvastatin (10 mg/d) significantly decreased hsCRP in patients overall, and MCP-1 was also decreased in women. These findings suggest the possibility that atorvastatin provides an anti-inflammatory effect even at a low dose.
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PMID:The effect of low-dose atorvastatin on circulating monocyte chemoattractant protein-1 in patients with type 2 diabetes complicated by hyperlipidemia. 1612 34

Different degrees of beta-cell failure and apoptosis are present in type 1 and type 2 diabetes. It has been recently suggested that high glucose-induced beta-cell apoptosis in type 2 diabetes shares a final common pathway with type 1 diabetes, involving interleukin-1beta (IL-1beta) production by beta-cells, nuclear factor-kappaB (NF-kappaB) activation, and death via Fas-FasL. The aim of this study was to test whether human islet exposure to high glucose in vitro, or to the type 2 diabetes environment in vivo, induces IL-1beta expression and consequent activation of NF-kappaB-dependent genes. Human islets were isolated from five normoglycemic organ donors. The islets were cultured for 48 h to 7 days at 5.6, 11, or 28 mmol/l glucose. For comparative purposes, islets were also exposed to IL-1beta. Gene mRNA expression levels were assessed by real-time RT-PCR in a blinded fashion. Culture of the human islets at 11 and 28 mmol/l glucose induced a four- to fivefold increase in medium insulin as compared with 5.6 mmol/l glucose, but neither IL-1beta nor IL-1 receptor antagonist (IL-1ra) expression changed. IL-1beta and IL-1ra protein release to the medium was also unchanged. Stimulated human monocytes, studied in parallel, released >50-fold more IL-1beta than the islets. There was also no glucose-induced islet Fas expression. Expression of the NF-kappaB-dependent genes IkappaB-alpha and monocyte chemoattractant protein (MCP)-1 was induced in human islets by IL-1beta but not by high glucose. In a second set of experiments, human islets were isolated from seven type 2 diabetic patients and eight control subjects. The findings on mRNA levels were essentially the same as in the in vitro experiments, namely the in vivo diabetic state did not induce IL-1beta, Fas, or MCP-1 expression in human islets, and also did not modify IL-1ra expression. The present findings suggest that high glucose in vitro, or the diabetic milieu in vivo, does not induce IL-1beta production or NF-kappaB activation in human islets. This makes it unlikely that locally produced IL-1beta is an important mediator of glucotoxicity to human islets and argues against the IL-1beta-NF-kappaB-Fas pathway as a common mediator for beta-cell death in type 1 and type 2 diabetes.
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PMID:Is there a role for locally produced interleukin-1 in the deleterious effects of high glucose or the type 2 diabetes milieu to human pancreatic islets? 1624 50

The endothelium releases multiple mediators, not only regulators of vasomotor function but also important physiological and pathophysiological inflammatory mediators. Endothelial dysfunction is caused by chronic exposure to various stressors such as oxidative stress and modified low-density lipoprotein (LDL) cholesterol, resulting in impaired nitric oxide (NO) production and chronic inflammation. Biomechanical forces on the endothelium, including low shear stress from disturbed blood flow and hypertension, are also important causes of endothelial dysfunction. These processes seem to be augmented in patients with diabetes. In states of insulin resistance and in type 2 diabetes insulin signalling is impaired. Increased vascular inflammation, including enhanced expression of interleukin- 6 (IL-6), vascular cellular adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein (MCP- 1) are observed, as is a marked decrease in NO bioavailability. Furthermore, hyperglycaemia leads to increased formation of advanced glycation end products (AGE), which quench NO and impair endothelial function. In summary, during the development of diabetes a number of biochemical and mechanical factors converge on the endothelium, resulting in endothelial dysfunction and vascular inflammation. In the presence of insulin resistance, these processes are potentiated and they provide a basis for the macrovascular disease seen in diabetes.
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PMID:The endothelium and vascular inflammation in diabetes. 1765 40

Arterial stiffness is an independent risk factor for cardiovascular events in diabetic patients, and it can be assessed by measuring pulse wave velocity (PWV). We investigated the degree of arterial stiffness in diabetic patients with coronary artery disease (CAD) and the effect of the proliferator-activated receptor gamma (PPAR-gamma) agonist rosiglitazone on arterial stiffness in the potential mechanism of anti-arteriosclerosis in patients with type 2 diabetes mellitus and CAD. The 123 participants were divided into 3 groups: healthy controls (n = 36), diabetic patients (n = 41), and diabetic patients with CAD (n = 46). Forty-six diabetic patients with CAD were randomly divided into 2 groups: untreated diabetic patients with CAD and diabetic patients with CAD treated with 4 mg/d of rosiglitazone (n = 25) for 12 weeks. Pulse wave velocity was measured before treatment and at 12-week follow-up. Baseline PWV was significantly higher in patients with diabetes, diabetes and CAD, and diabetes and CAD with treatment as compared with the healthy control group (1,633 +/- 37.3, 1,669 +/- 53.8, 1,615 +/- 44.4, and 1,360 +/- 39.9 cm/s, respectively, P < .001). Pulse wave velocity in the rosiglitazone-treated group was significantly reduced, from 1,615 +/- 44.4 to 1,525 +/- 43.1 cm/s, after 12-week treatment, Furthermore, PWV was significantly decreased in the rosiglitazone-treated group compared with untreated group after 12 weeks (1525 +/- 43.1 and 1,670 +/- 41.3 cm/s, respectively). Pulse wave velocity in the untreated group did not differ from baseline levels after 12 weeks. In addition, plasma C-reactive protein level was decreased significantly in the rosiglitazone-treated group compared with values at baseline and for the untreated group after 12 weeks (0.73 +/- 0.09, 1.71 +/- 0.24, and 1.33 +/- 0.29 mg/L, respectively). Plasma level of monocyte chemoattractant protein 1 was decreased in the rosiglitazone group compared with the level at baseline (392 +/- 42 and 273 +/- 40 pg/mL, respectively). Moreover, the decrease in PWV was associated linearly both with improved homeostasis model assessment of insulin resistance and with decreased C-reactive protein level after PPAR-gamma agonist treatment. In conclusion, PPAR-gamma agonist rosiglitazone treatment may significantly decrease arterial stiffness in diabetic patients with CAD. Proliferator-activated receptor gamma agonists may play an important role in protecting against arteriosclerosis by normalizing the metabolic disorders and depressing chronic inflammation of the vascular system in patients with type 2 diabetes mellitus and serious vascular disease.
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PMID:Peroxisome proliferator-activated receptor gamma agonist improves arterial stiffness in patients with type 2 diabetes mellitus and coronary artery disease. 1788 51

Chronic low-grade inflammation characterized by adipose tissue macrophage accumulation and abnormal cytokine production is a key feature of obesity and type 2 diabetes. Adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, induced by cytokines, has been shown to play an essential role in the early events during macrophage infiltration into adipose tissue. In this study we investigated the effects of resveratrol upon both tumor necrosis factor (TNF)-alpha-induced MCP-1 gene expression and its underlying signaling pathways in 3T3-L1 adipocytes. Resveratrol was found to inhibit TNF-alpha-induced MCP-1 secretion and gene transcription, as well as promoter activity, which based on down-regulation of TNF-alpha-induced MCP-1 transcription. Nuclear factor (NF)-kappaB was determined to play a major role in the TNF-alpha-induced MCP-1 expression. Further analysis showed that resveratrol inhibited DNA binding activity of the NF-kappaB complex and subsequently suppressed NF-kappaB transcriptional activity in TNF-alpha-stimulated cells. Finally, the inhibition of MCP-1 may represent a novel mechanism of resveratrol in preventing obesity-related pathologies.
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PMID:Anti-inflammatory effect of resveratrol on TNF-alpha-induced MCP-1 expression in adipocytes. 1829 Oct 98

Although metabolic derangement plays a central role in diabetic nephropathy, a better understanding of secondary mediators of injury may lead to new therapeutic strategies. Expression of macrophage migration inhibitory factor (MIF) is increased in experimental diabetic nephropathy, and increased tubulointerstitial mRNA expression of its receptor, CD74, has been observed in human diabetic nephropathy. Whether CD74 transduces MIF signals in podocytes, however, is unknown. Here, we found glomerular and tubulointerstitial CD74 mRNA expression to be increased in Pima Indians with type 2 diabetes and diabetic nephropathy. Immunohistochemistry confirmed the increased glomerular and tubular expression of CD74 in clinical and experimental diabetic nephropathy and localized glomerular CD74 to podocytes. In cultured human podocytes, CD74 was expressed at the cell surface, was upregulated by high concentrations of glucose and TNF-alpha, and was activated by MIF, leading to phosphorylation of extracellular signal-regulated kinase 1/2 and p38. High glucose also induced CD74 expression in a human proximal tubule cell line (HK2). In addition, MIF induced the expression of the inflammatory mediators TRAIL and monocyte chemoattractant protein 1 in podocytes and HK2 cells in a p38-dependent manner. These data suggest that CD74 acts as a receptor for MIF in podocytes and may play a role in the pathogenesis of diabetic nephropathy.
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PMID:The MIF receptor CD74 in diabetic podocyte injury. 1884 89

Inflammation and insulin resistance associated with visceral obesity are important risk factors for the development of type 2 diabetes, atherosclerosis, and the metabolic syndrome. The 12/15-lipoxygenase (12/15-LO) enzyme has been linked to inflammatory changes in blood vessels that precede the development of atherosclerosis. The expression and role of 12/15-LO in adipocytes have not been evaluated. We found that 12/15-LO mRNA was dramatically upregulated in white epididymal adipocytes of high-fat fed mice. 12/15-LO was poorly expressed in 3T3-L1 fibroblasts and was upregulated during differentiation into adipocytes. Interestingly, the saturated fatty acid palmitate, a major component of high fat diets, augmented expression of 12/15-LO in vitro. When 3T3-L1 adipocytes were treated with the 12/15-LO products, 12-hydroxyeicosatetranoic acid (12(S)-HETE) and 12-hydroperoxyeicosatetraenoic acid (12(S)-HPETE), expression of proinflammatory cytokine genes, including tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), and IL-12p40, was upregulated whereas anti-inflammatory adiponectin gene expression was downregulated. 12/15-LO products also augmented c-Jun N-terminal kinase 1 (JNK-1) phosphorylation, a known negative regulator of insulin signaling. Consistent with impaired insulin signaling, we found that insulin-stimulated 3T3-L1 adipocytes exhibited decreased IRS-1(Tyr) phosphorylation, increased IRS-1(Ser) phosphorylation, and impaired Akt phosphorylation when treated with 12/15-LO product. Taken together, our data suggest that 12/15-LO products create a proinflammatory state and impair insulin signaling in 3T3-L1 adipocytes. Because 12/15-LO expression is upregulated in visceral adipocytes by high-fat feeding in vivo and also by addition of palmitic acid in vitro, we propose that 12/15-LO plays a role in promoting inflammation and insulin resistance associated with obesity.
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PMID:12/15-lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes. 1952 44

The aim of the study was to evaluate the long-term effect of rosiglitazone and metformin monotherapy with medical nutrition treatment (MNT) and of MNT alone on arterial stiffness, serum monocyte chemoattractant protein (MCP)-1 and matrix metalloproteinase (MMP)-9 in drug naive patients with type 2 diabetes mellitus. Fifty type 2 diabetic patients were randomized to receive rosiglitazone 4 mg/day (n=19) or metformin 850 mg/day (n=16) with MNT or MNT alone (n=15), for 52 weeks. Arterial stiffness was assessed by using large and small artery elasticity index (SAEI and LAEI, respectively). SAEI, LAEI, serum MCP-1 and MMP-9 levels were measured at baseline and following 52 weeks of treatment. SAEI was improved only in the rosiglitazone group, and the difference was still statistically significant when the three groups were compared (p=0.024). There were no differences in LAEI in inter- and intragroup comparisons at the end of the study. Serum MMP-9 levels were decreased in the metformin (-13.5+/-34.8%, p=0.02) and rosiglitazone (-27.2+/-51.0%, p=0.023) groups compared with baseline values, whereas no significant change was seen in serum MCP-1 levels. These results suggest that rosiglitazone monotherapy has favorable effects on arterial stiffness compared with metformin monotherapy independent of glycemic control.
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PMID:Effect of rosiglitazone, metformin and medical nutrition treatment on arterial stiffness, serum MMP-9 and MCP-1 levels in drug naive type 2 diabetic patients. 1967 6


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