Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial dysfunction, insulin resistance, and elevated levels of circulating proinflammatory markers are among the earliest detectable abnormalities in people at risk for atherosclerosis. Accelerated atherosclerosis is a leading contributor to morbidity and mortality in type 2 diabetes mellitus, a complex genetic disorder. Therefore, we hypothesized that normoglycemic offspring of patients with type 2 diabetes mellitus (NOPD) may have impaired vascular and metabolic function related to an enhanced proinflammatory state. We compared NOPD (n = 51) with matched healthy control subjects without family history of diabetes (n = 35). Flow- and nitroglycerin-mediated brachial artery vasodilation were assessed by ultrasound to evaluate endothelium-dependent and -independent vascular function. Each subject also underwent an oral glucose tolerance test to evaluate metabolic function. Fasting levels of plasma adiponectin and circulating markers of inflammation (high-sensitivity C-reactive protein, CD40 ligand, interleukin 1beta, tumor necrosis factor alpha, vascular cell adhesion molecule 1, and intracellular adhesion molecule) were measured. Both NOPD and the control group had fasting glucose and insulin levels well within the reference range. However, results from oral glucose tolerance test and quantitative insulin sensitivity check index revealed that NOPD were insulin resistant with significantly impaired flow- and nitroglycerin-mediated dilation compared with the control group. Adiponectin levels were lower, whereas many circulating markers of inflammation were higher, in NOPD compared with the control group. Normoglycemic offspring of patients with type 2 diabetes mellitus have impaired vascular and metabolic function accompanied by an enhanced proinflammatory state that may contribute to their increased risk of diabetes and its vascular complications.
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PMID:Vascular, metabolic, and inflammatory abnormalities in normoglycemic offspring of patients with type 2 diabetes mellitus. 1729 32

Adrenal incidentalomas (AIs) have been associated with an increased incidence of several cardiovascular risk factors, similar to overt Cushing syndrome. Data about the involvement of the adipokines in the development of insulin resistance and atherosclerosis in AI are completely lacking. The aim of the present study was to evaluate plasma interleukin 6 (IL-6), adiponectin, resistin, tumor necrosis factor alpha (TNF-alpha), and monocyte chemoattractant protein 1 (MCP-1) levels in patients with AI. Plasma IL-6, adiponectin, resistin, TNF-alpha, and MCP-1 levels were measured in 20 healthy subjects (6 males; 14 females; age, 58.5 +/- 2.2 years; body mass index, 28.1 +/- 0.9 kg/m(2)) and in 20 patients (5 males; 15 females; age, 57.9 +/- 2.0 years; body mass index, 28.0 +/- 0.8 kg/m(2)) with AI and typical computed tomographic features of cortical adenoma, who were not affected by diabetes mellitus, hypertension, or other relevant diseases. All patients underwent anthropometric measurements and determination of basal corticotropin, cortisol, and urinary free cortisol excretion. Overnight dexamethasone test and 250-microg corticotropin test were performed in all cases. A subclinical Cushing syndrome was found in 3 patients, whereas the others had apparently nonfunctioning masses. Plasma IL-6, adiponectin, resistin, TNF-alpha, and MCP-1 levels were higher in patients than in controls (64.4 +/- 2.8 vs 5.5 +/- 0.6 pg/mL, 13.7 +/- 1.3 vs 3.6 +/- 0.5 microg/mL, 12.5 +/- 1.9 vs 5.1 +/- 0.2 ng/mL, 27.0 +/- 1.5 vs 22.2 +/- 1.5 pg/mL, 172.5 +/- 20.0 vs 104.4 +/- 19.5 pg/mL, respectively; P < .05) and apparently not affected by the presence of visceral obesity. Plasma IL-6 levels were negatively correlated with urinary free cortisol (r = -0.461, P < .05), and TNF-alpha levels were positively correlated with cortisol after the administration of 1 mg dexamethasone (r = 0.636, P < .01). In conclusion, patients with AI may show increased levels of adipokines (apparently not related to the presence of diabetes, hypertension, or obesity), which may be affected by the presence of the adrenal adenoma. For some adipokines, a direct production from the adrenal gland may be hypothesized even if other studies are needed to better investigate the role of adipokines in states of altered cortisol secretion.
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PMID:Adipokine levels and cardiovascular risk in patients with adrenal incidentaloma. 1744 45

Thiazolidinediones, also known as glitazones, represent a relatively new class of medication used for glycemic control in patients with type II diabetes mellitus. These drugs interact with the peroxisome proliferator-activated receptor gamma, a member of the nuclear receptor superfamily, which in turn heterodimerizes with retinoid X receptors to stimulate gene transcription. At a physiologic level, glitazones stimulate adipocyte differentiation, enhance insulin-sensitive glucose uptake by muscle and fat cells, suppress angiogenesis, inhibit tumor cell growth, and normalize keratinocyte differentiation. They have also demonstrated the capacity to diminish inflammatory cytokine production, most notably, that of tumor necrosis factor alpha. Patients with such disparate conditions as psoriasis, hirsutism, melanoma, angiosarcoma, lipodystrophy, and necrobiosis lipoidica have benefited from the administration of thiazolidinediones. Clinicians should become familiar with glitazones as they are experiencing a burgeoning use among patients with non-insulin-dependent diabetes mellitus and have demonstrated clinical efficacy in treating certain skin conditions.
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PMID:Thiazolidinediones in dermatology. 1755 May 51

Obesity is an alarming primary health problem and is an independent risk factor for type II diabetes, cardiovascular diseases, and hypertension. Although the pathologic mechanisms linking obesity with these co-morbidities are most likely multifactorial, increasing evidence indicates that altered secretion of adipose-derived signaling molecules (adipokines; e.g. adiponectin, leptin, and tumor necrosis factor alpha) and local inflammatory responses are contributing factors. Chemerin (RARRES2 or TIG2) is a recently discovered chemoattractant protein that serves as a ligand for the G protein-coupled receptor CMKLR1 (ChemR23 or DEZ) and has a role in adaptive and innate immunity. Here we show an unexpected, high level expression of chemerin and its cognate receptor CMKLR1 in mouse and human adipocytes. Cultured 3T3-L1 adipocytes secrete chemerin protein, which triggers CMKLR1 signaling in adipocytes and other cell types and stimulates chemotaxis of CMKLR1-expressing cells. Adenoviral small hairpin RNA targeted knockdown of chemerin or CMKLR1 expression impairs differentiation of 3T3-L1 cells into adipocytes, reduces the expression of adipocyte genes involved in glucose and lipid homeostasis, and alters metabolic functions in mature adipocytes. We conclude that chemerin is a novel adipose-derived signaling molecule that regulates adipogenesis and adipocyte metabolism.
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PMID:Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. 1763 25

We investigated whether atorvastatin, given in a dose to low to influence the lipid profile, has any effect on oxidative stress, inflammation and endothelial function under streptozotocin-induced diabetic conditions. Diabetes mellitus was induced in male Sprague Dawley rats by a single injection of streptozotocin. Rats were treated chronically with atorvastatin (50 mg/kg/day; p.o.) or vehicle until day 48 and compared with controls. NAD(P)H activity, protein expression nuclear factor-kappaBp65 (NF-kappaBp65) and phosphorylation of the extracellular signal-regulated kinase (ERK1/2) were assessed in the quadriceps muscle. Protein and mRNA levels of intracellular and vascular adhesion molecules (ICAM-1, VCAM-1) and cytokines were measured by Taqman or immunohistochemistry staining, respectively. Endothelial function was investigated in vivo using the autoperfused hind limb model. Diabetic groups displayed similar severe hyperglycemia. Untreated diabetic rats showed enhanced NAD(P)H activity, activation of the ERK1/2/NF-kappaBp65-pathway, enhanced expression of cytokines and cellular adhesion molecules and impaired vascular function. Low-dose therapy by atorvastatin did not alter the lipid profile but led to a reduction of NAD(P)H activity (-28%, P<0.05) associated with reduced protein expression of NF-kappaBp65 (-53%, P<0.05) and phosphorylation of its regulator mitogen-activated protein kinase (MAPK) ERK1/2 in diabetic rats. Also inflammatory markers were reduced after atorvastatin treatment indexed by reduced mRNA expression of VCAM-1 (-24%), tumor necrosis factor alpha (-59%) and interleukin 1beta (-50%) and reduced ICAM-1 (-81%) and VCAM-1 (-74%) positive staining. These beneficial effects were associated with improved endothelium-dependent vasodilatation (maximal vasodilatation: +101%; P<0.05). Lipid-independent anti-oxidative and anti-inflammatory effects of low-dose atorvastatin involving the ERK1/2/NF-kappaB-pathway are sufficient to improve endothelial function under experimental diabetic conditions.
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PMID:Low-dose treatment with atorvastatin leads to anti-oxidative and anti-inflammatory effects in diabetes mellitus. 1766 95

The aim of the study was to analyze the relation between early diabetic retinopathy and the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) in children with diabetes mellitus type 1. Two hundred and two children with diabetes mellitus type 1 aged 13.2+/-3.83 years and 85 healthy controls were analyzed. Patients were divided into two subgroups: children with retinopathy (Group 1, n=39) and children without retinopathy (Group 2, n=163). All the children had 24h urine albumin secretion rate, glycosylated hemoglobin HbA1c level, and C-reactive protein level measured, underwent 24h blood pressure monitoring and had ophthalmologic examination performed. Additionally, all the children had serum TNF-alpha, IL-6 and VEGF level measured using an ELISA test (Quantikine High Sensitivity Human). Statistically significant higher blood serum levels of HbA1c, VEGF, TNF-alpha and IL-6 were found in the Group 1 in comparison with the Group 2. Additionally, the children of the Group 1 showed statistically significant correlation between serum VEGF and serum TNF-alpha (R=0.35, p=0.000), CRP level (R=0.23, p=0.006), 24h albumin urine secretion rate (R=0.45, p=0.000) and duration of the disease (R=0.26, p=0.002). The results of the current study suggest that there is a relationship between VEGF, TNF-alpha, IL-6 and the development of the diabetic retinopathy in children with diabetes mellitus type 1.
Diabetes Res Clin Pract 2008 Jan
PMID:The role of vascular endothelial growth factor, tumor necrosis factor alpha and interleukin-6 in pathogenesis of diabetic retinopathy. 1771 75

The objective of this study was to assess the capacity of different criteria of metabolic syndrome (MetS) to identify risks of coronary heart diseases (CHDs) and related changes of adipocytokines in postmenopausal women. A cross-sectional study was carried out in 225 community-dwelling, elderly postmenopausal Chinese women (age, 66.77+/-5.09 years) without hormone replacement therapy (HRT). Baseline data such as blood pressure, body mass index (BMI), serum lipid profiles, and fasting glucose were analyzed, and insulin sensitivity was estimated via the homeostasis model assessment for insulin resistance. Serum tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), and adiponectin were measured simultaneously. The prevalence of MetS identified by the Third Report of the National Cholesterol Education Programme Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, the International Diabetes Federation (IDF), the Chinese Diabetes Society (CDS), and the Japanese Society of Internal Medicine (JPN) were 27.31%, 37.34%, 23.29%, and 13.65%, respectively. No significant differences of baseline data were found among different MetS groups, except for a significant higher waist circumference in the JPN-MetS group as compared with other MetS groups. The prevalence of confirmed CHD in the four MetS groups were 26.2%, 18.6%, 26.9%, and 32%, respectively. Odds ratios for CHD were 1.905 (95% CI=1.273-2.851), 1.208 (95% CI=0.778-1.876), 1.997 (95% CI=1.238-3.221), and 2.336 (95% CI=1.119-4.876), respectively. The JPN-MetS group had higher levels of TNFalpha and IL-6, whereas the CDS-MetS group correlated better with lower adiponectin levels. The IDF definition for MetS is the most sensitive one with regard to metabolic disorders, whereas JPN and CDS definitions correlate better with CHD and changes of adipocytokines among the four criteria studied.
J Diabetes Complications
PMID:Risks of CHD identified by different criteria of metabolic syndrome and related changes of adipocytokines in elderly postmenopausal women. 1782 56

The fact that fat issue is an endocrine gland secreting several hormones participating in the pathogenesis of type 2 diabetes mellitus (DM2) is universally recognized. Fat issue secretes leptin, tumor necrosis factor alpha, resistin, adiponectin, interleukin-6, free fatty acids, visfatin, omentin, perilipin, and other substances that influence the condition of insulinoresistance, one of the main factors responsible for DM2. Subcutaneous fat and visceral depot fat tissue differ in the spectrum of hormones they produce; the list of these hormones is presented in the article. The presence of abdominal or visceral obesity is combined with significant insulinoresistance, which, in its turn, increases the risk of vascular complications of diabetes. The article also cover the participation of other mechanisms - insulin secretion defect, oxidation stress, low secretion of glucagon-like peptide 1, apoptosis, an increased quantity of amyloid and the fl-cell pull in the pancreatic island--in DM2 pathogenesis. The authors present data on the secretion of leptin, resistin, adiponectin, and tumor necrosis factor a, as well as the condition of the functional activity of beta-cells and the degree of insulinoresistance in 30 DM2 patients receiving dietotherapy.
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PMID:[The role of the fat tissue and its hormones in the mechanisms of insulin resistance and the development of type 2 diabetes mellitus]. 1788 4

Adiponectin can improve both glucose metabolism and insulin resistance via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Activated AMPK phosphorylates a variety of intracellular proteins, including acetyl coenzyme A carboxylase (ACC) that is involved in fatty acid oxidation. Adenosine monophosphate-activated protein kinase increases glucose transport by stimulating the translocation of glucose transporter 4 (GLUT4) to the sarcolemma in the heart. Adiponectin exerts its effect through adiponectin receptors, which are predominantly expressed in the liver and skeletal muscle. It is unknown whether the cardiac expression of adiponectin and its receptors is changed in diabetic rats. In the present study, we investigated the protein expression of adiponectin and its receptors in streptozotocin (STZ)-induced diabetic rat hearts. We also explored whether the levels of AMPK, ACC, and GLUT4 will be altered with the changed adiponectin and its receptors in STZ diabetic rat hearts. Plasma and cardiac adiponectin levels were measured by radioimmunoassay. Plasma and cardiac interleukin 6 and plasma tumor necrosis factor alpha (TNF-alpha) were assayed by enzyme-linked immunosorbent assay. Cardiac adiponectin receptors, AMPK-alpha, ACC, GLUT4, and TNF-alpha were analyzed by Western blot in control and STZ diabetic rats. The plasma adiponectin level was decreased, but the cardiac protein expression of adiponectin receptor 1 was increased in diabetic rats. There was no difference in the cardiac adiponectin level and the cardiac adiponectin receptor 2 protein expression between control and diabetic rats. The phosphorylation of AMPK-alpha and protein expression of GLUT4 were decreased, but the phosphorylation of ACC was unchanged in diabetic rat hearts. Plasma and cardiac levels of interleukin 6 and TNF-alpha were increased in diabetic rats. In conclusion, STZ-induced diabetes up-regulates adiponectin receptors in the heart. Despite an increase in cardiac adiponectin receptor 1 expression, there is an increased cardiac inflammatory response and a decreased GLUT4 protein expression associated with a reduction in circulating adiponectin.
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PMID:Cardiac expression of adiponectin and its receptors in streptozotocin-induced diabetic rats. 1788 46

Neonatal diet may influence the development of type 1 diabetes (T1D) in susceptible individuals through an intestinal mucosal inflammatory response, resulting in loss of self-tolerance. We tested the hypothesis that formula feeding during the neonatal period accelerates the development of T1D in diabetes-prone BioBreeding (BBDP) rats through regulation of CD4+CD25+ regulatory T lymphocytes (T(reg)) and anti-inflammatory cytokines. BBDP rat pups fed rat milk substitute (RMS) via a "pup-in-the cup" system were compared with mother-fed (MF) rats. The spleen and thymus were analyzed for Foxp3-expressing CD4+/CD25+ T cells. Multiplex enzyme-linked immunosorbent assays (ELISAs) were performed to measure cytokine-induced neutrophil chemoattractant (CINC), tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-10, and IL-18. Diabetes-free survival, time of disease onset, and T(reg)/total T lymphocyte ratios were not different. MF pups had higher ileal CINC (p < 0.001) and IL-18 (p = 0.002), but no differences in the liver. There were no differences in ileal cytokine concentrations of 75-d-old rats, but the formula-fed rats had greater liver TNF-alpha (p < 0.001), IFN-gamma, and IL-4 (p < 0.01) and lower IL-10 (p = 0.002) compared with MF animals. Formula versus maternal milk altered the hepatic cytokine profile at 75 d toward an inflammatory pattern but did not result in altered T(reg) cell frequencies or the development of T1D.
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PMID:Neonatal formula feeding leads to immunological alterations in an animal model of type 1 diabetes. 1809 54


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