Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistin is a newly discovered adipocyte hormone. It is related to resistin-like molecules alpha, beta and gamma in structure and function. Resistin is produced by white and brown adipose tissues but has also has been identified in several other tissues, including the hypothalamus, pituitary and adrenal glands, pancreas, gastrointestinal tract, myocytes, spleen, white blood cells and plasma. The tissue level of resistin is decreased by insulin, cytokines such as tumour necrosis factor alpha, endothelin-1 and increased by growth and gonadal hormones, hyperglycaemia, male gender and some proinflammatory cytokines, such as interleukin-6 and lipopolysaccharide. Resistin antagonizes insulin action, and it is downregulated by rosiglitazone and peroxisome proliferator-activated receptor gamma agonists. Since evidence of a direct link between resistin genotype and human diabetes is still weak, more molecular, physiological and clinical studies are needed to determine the role of resistin in the aetiology of type 2 diabetes.
 ...
PMID:An update on the biology and physiology of resistin. 1552 56

S100A12, also called EN-RAGE (extracellular newly identified receptor for advanced glycation end products binding protein) or calcium-binding protein in amniotic fluid-1, is a ligand for RAGE. It has been shown that S100A12 induces adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in the vascular endothelial cell and mediates migration and activation of monocytes/macrophages through RAGE binding and that infusion of lipopolysaccharide into mice causes time-dependent increase of S100A12 in the plasma. Therefore, circulating S100A12 protein may be involved in chronic inflammation in the atherosclerotic lesion. In this study, we developed an ELISA system that uses specific monoclonal antibodies against recombinant human S100A12 to measure plasma S100A12 levels in patients with diabetes. On using our S100A12 ELISA system, the coefficients of variation of intra- and interassay were less than 4 and 9%, respectively. The analytical lower detection limit was 0.2 ng/ml. When plasma S100A12 levels were measured by this system, the concentrations were more than twice as high in the patients with diabetes, compared with those without. Using univariate analysis in all subjects, plasma S100A12 concentrations correlated with hemoglobin A1c, fasting glucose, high-sensitivity C-reactive protein and white blood cell count. Stepwise multiple regression analyses, however, revealed that only white blood cell count and hemoglobin A1c remained significant independent determinants of plasma S100A12 concentration. These results suggest that plasma S100A12 protein levels are regulated by factors related to subclinical inflammation and glucose control in patients with type 2 diabetes.
 ...
PMID:Increased plasma S100A12 (EN-RAGE) levels in patients with type 2 diabetes. 1553 92

Impaired course of inflammation is a likely mechanism behind a number of diabetic complications. The present study was undertaken to investigate lipopolysaccharide-induced production of tumour necrosis factor (TNF)-alpha in monocytes from patients with type 2 diabetes and to assess its relationship with diabetes-associated metabolic abnormalities. Monocytic TNF-alpha mRNA production was lower in the diabetic participants compared to their corresponding controls. Diabetic subjects who had been receiving simvastatin treatment had TNF-alpha mRNA production similar to that of the healthy participants. The release of TNF-alpha from diabetic cells correlated negatively with serum levels of apolipoprotein B (apoB) (R = -0.755, P = 0.001), total plasma cholesterol (R = - 0.702, P = 0.002) and the presence of retinopathy (R = -0.572, P = 0.021). No such associations were found in the control subjects. In a multiple linear regression model, only the level of apoB and diabetes duration demonstrated significant effects on the release of TNF-alpha, with apoB alone accounting for 57% of the variation. We conclude that production of TNF-alpha mRNA in response to the bacterial stimulant is compromised in poorly controlled type 2 diabetes. Lipid abnormalities are associated with the observed defect. Impaired cytokine production represents a significant defect in the functioning of the immune system and may contribute to aberrations in the course of inflammation in the diabetic state.
 ...
PMID:Release of TNF-alpha from in vitro-stimulated monocytes is negatively associated with serum levels of apolipoprotein B in patients with type 2 diabetes. 1554 Oct 48

Comparing macrophage-derived cytokine and nitric oxide (NO) profiles in type I and type II diabetes mellitus (DM); and determining whether thymoquinone (TQ) has any modulatory effect were the main objectives of the present study. Peritoneal macrophages have been collected from Otsuka Long-Evans Tokushima Fatty (OLETF) as a model for type II DM and its control Long-Evans Tokushima Otsuka (LETO) rats, as well as from streptozotocin (STZ)-injected LETO ones as a model for type I DM. The cells were cultured and incubated with or without TQ (10 microM) in the absence or presence of lipopolysaccharide (LPS; 1 microg/ml). The same parameters have been also assessed in sera of the used animals with or without TQ treatment (3 mg/kg) under both LPS-stimulated (10 mg/kg) and unstimulated conditions. Nitrite, IL-1beta and TNF-alpha were significantly higher in macrophage supernatants and sera of the acutely affected STZ-LETO rats either with or without LPS stimulation compared to corresponding controls. On the other hand, chronically diabetic OLETF rats' macrophage supernatants showed significant decreases of IL-1beta and TNF-alpha levels upon LPS stimulation or even without stimulation (IL-1beta); and insignificant increase in nitrite concentration, which turned significant upon LPS stimulation. Sera of these animals, however, showed significant increase in TNF-alpha level. TQ normalised the elevated nitrite and cytokine profiles both in vitro and in vivo, yet had no significant effect on the already decreased parameters in chronically affected OLETF rats. These data suggest that there is a tendency for macrophage inflammatory products to increase in acute type I and to decrease in chronic type II DM; and that TQ has the potential to normalise the elevated levels of these macrophage-derived inflammatory mediators.
 ...
PMID:Macrophage-derived cytokine and nitric oxide profiles in type I and type II diabetes mellitus: effect of thymoquinone. 1586 10

Rosiglitazone, an agonist of peroxisome proliferator-activated receptor-gamma (PPAR gamma ), is an insulin-sensitizing antidiabetic agent and inhibits restenosis in animal blood vessels. However, its benefit for patients with type 2 diabetes and coronary artery disease (CAD) after percutaneous coronary intervention is unknown. Patients with diabetes and CAD who had undergone percutaneous coronary intervention were randomized to either receive or not receive rosiglitazone (4 mg/d) for 6 months. After 6 months of rosiglitazone treatment, the plasma levels of fasting glucose and insulin and those of hemoglobin A1C and homeostasis model assessment of insulin resistance were significantly decreased in the rosiglitazone group as compared with baseline levels and those in the control group. After 2 and 6 months of rosiglitazone treatment, the plasma level of high-density lipoprotein was significantly increased in the rosiglitazone group. In addition, plasma levels of monocyte chemoattractant protein-1 and C-reactive protein and hyperresponsiveness of low-dose lipopolysaccharide-induced monocyte chemoattractant protein-1 secretion from monocytes were reduced. Furthermore, the occurrence of coronary events was significantly decreased in the rosiglitazone group at 6-month follow-up. Our data indicate that rosiglitazone may protect the vascular wall through not only improving the features of metabolic disorders but also reducing proinflammatory responses and the occurrence of coronary events in patients with diabetes and CAD after percutaneous coronary intervention.
 ...
PMID:Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduces clinical inflammatory responses in type 2 diabetes with coronary artery disease after coronary angioplasty. 1587 88

Resistin, a recently discovered 92 amino acid protein involved in the development of insulin resistance, has been associated with obesity and type 2 diabetes. The elevated serum resistin in human diabetes is often associated with a pro-inflammatory milieu. However, the role of resistin in the development of inflammation is not well understood. Addition of recombinant human resistin protein (hResistin) to macrophages (both murine and human) resulted in enhanced secretion of pro-inflammatory cytokines, TNF-alpha and IL-12, similar to that obtained using 5 microg/ml lipopolysaccharide. Both oligomeric and dimeric forms of hResistin were able to activate these cytokines suggesting that the inflammatory action of resistin is independent of its conformation. Heat denatured hResistin abrogated cytokine induction while treatment of recombinant resistin with polymyxin B agarose beads had no effect thereby ruling out the role of endotoxin in the recombinant hResistin mediated cytokine induction. The pro-inflammatory nature of hResistin was further evident from the ability of this protein to induce the nuclear translocation of NF-kappaB transcription factor as seen from electrophoretic mobility shift assays. Induction of TNF-alpha in U937 cells by hResistin was markedly reduced in the presence of either dominant negative IkappaBalpha plasmid or PDTC, a pharmacological inhibitor of NF-kappaB. A protein involved in conferring insulin resistance is also a pro-inflammatory molecule that has important implications.
 ...
PMID:Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway. 1603 94

Recent prospective studies indicate endothelial dysfunction and increased risk for cardiovascular events in patients with serological evidence of multiple infections. Soluble CD14 (sCD 14) plays a key role in the neutralization of lipopolysaccharide (LPS), a well-established bacterial product inducing endothelial dysfunction. Insulin resistance was recently identified as a significant factor influencing circulating sCD 14 concentration. Thus, we investigated the association of circulating sCD14 and endothelial dysfunction in subjects with well-established insulin resistance (patients with type 2 diabetes, n = 40) compared to control non-diabetic subjects (n = 100). To further explore the underlying mechanisms, we also analysed C-reactive protein and circulating NO2-/NO3- and cyclic GMP in the diabetic group. Serum sCD 14 concentration (ELISA) was found to be differently associated with endothelium-dependent vasodilatation (EDVD, high-resolution ultrasound) in diabetic and non-diabetic subjects. In nondiabetic subjects, serum sCD14 and C-reactive protein correlated negatively with EDVD (r = -0.21, p = 0.03, and r = -0.21, p = 0.03, respectively). In a partial correlation analysis, these associations remained significant after controlling for age and weight (sCD 14 and EDVD, r = -0.23, p = 0.023; C-reactive protein and EDVD, r = -0.21, p = 0.03; sCD14 and C-reactive protein, r = 0.30, p = 0.002). In contrast, sCD 14 was positively associated with EDVD in type 2 diabetic patients (r = 0.37, p = 0.019,). Interestingly, sCD14 was also associated with NO2-/NO3- in this group (r = 0.62, p = 0.001, n = 22). EDVD also correlated with cyclic GMP (r = 0.47, p = 0.03, n = 22). In summary, circulating sCD 14 is associated with endothelial function. While in non-diabetic subjects sCD14 behaves as an acute phase reactant, its role in type 2 diabetic patients should be further clarified. These findings need to be confirmed in further studies with larger number of patients.
 ...
PMID:Opposite relationship between circulating soluble CD14 concentration and endothelial function in diabetic and nondiabetic subjects. 1626 80

Nonalcoholic fatty liver disease is a relatively new hepatic sequela of obesity and type 2 diabetes. The pathogenesis of liver injury and disease progression in nonalcoholic fatty liver disease, however, is poorly understood. The present study examined the hypothesis that the composition of fatty acids in the steatotic liver promotes liver injury. Using dietary models of hepatic steatosis characterized by similar accumulation of total triglyceride but different composition of fatty acids, we show that hepatic steatosis characterized by increased saturated fatty acids is associated with increased liver injury and markers of endoplasmic reticulum stress (e.g. X-box binding protein-1 mRNA splicing and glucose-regulated protein 78 expression). These changes preceded and/or occurred independently of obesity and differences in leptin, TNFalpha, insulin action, and mitochondrial function. In addition, hepatic steatosis characterized by increased saturated fatty acids reduced proliferative capacity in response to partial hepatectomy and increased liver injury in response to lipopolysaccharide. These data suggest that the composition of fatty acids in the steatotic liver is an important determinant of susceptibility to liver injury.
 ...
PMID:Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis. 1626 65

We examined the effect of negative affect on changes in stimulated secretion of cytokines by blood monocytes and determined whether insulin resistance (IR), as indexed by the Homeostasis Model Assessment (HOMA), moderated these associations in 58 healthy men (aged 18-65 years). Blood samples and ratings of negative affect were collected at rest and 15min following subjects' participation in the Anger Recall Interview (ARI). Assessment of lipopolysaccharide (LPS)-stimulated secretion of IL-1beta, IL-6, and TNF-alpha was accomplished by ELISA of supernatant. Regression models controlling for age, body mass index, and race/ethnicity revealed that higher HOMA-IR values were associated with larger stress-induced increases in IL-1beta and TNF-alpha (p<.05). Furthermore, arousal of negative affect during the ARI was differentially associated with stress-induced changes in stimulated secretion of TNF-alpha and IL-6 as a function of HOMA-IR (p<.05). Increases in stimulated cytokine secretion were associated with arousal of negative affect, but only among men with higher HOMA-IR values. Among men with lower HOMA-IR values, arousal of negative affect was associated with diminished cytokine secretion. Collectively, these data suggest that the HOMA-IR moderates the impact that arousal of negative affect has on the ability of blood monocytes to secrete inflammatory cytokines in response to LPS. Stress-induced increases in cytokine secretion among high HOMA-IR men are consistent with the role of inflammation in cardiovascular disease, hypertension, type 2 diabetes as well as the metabolic syndrome and underscore the relevance of negative affect in the etiology of these inflammatory conditions.
 ...
PMID:Increases in stimulated secretion of proinflammatory cytokines by blood monocytes following arousal of negative affect: the role of insulin resistance as moderator. 1628 46

The diabetic heart shows increased fibrosis, which impairs cardiac function. Endothelin (ET)-1 and nuclear factor-kappaB (NF-kappaB) interactively regulate fibroblast growth. We have recently demonstrated that Punica granatum flower (PGF), a Unani anti-diabetic medicine, is a dual activator of peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma, and improves hyperglycemia, hyperlipidemia, and fatty heart in Zucker diabetic fatty (ZDF) rat, a genetic animal model of type 2 diabetes and obesity. Here, we demonstrated that six-week treatment with PGF extract (500 mg/kg, p.o.) in Zucker diabetic fatty rats reduced the ratios of van Gieson-stained interstitial collagen deposit area to total left ventricular area and perivascular collagen deposit areas to coronary artery media area in the heart. This was accompanied by suppression of overexpressed cardiac fibronectin and collagen I and III mRNAs. Punica granatum flower extract reduced the up-regulated cardiac mRNA expression of ET-1, ETA, inhibitor-kappaBbeta and c-jun, and normalized the down-regulated mRNA expression of inhibitor-kappaBalpha in Zucker diabetic fatty rats. In vitro, Punica granatum flower extract and its components oleanolic acid, ursolic acid, and gallic acid inhibited lipopolysaccharide-induced NF-kappaB activation in macrophages. Our findings indicate that Punica granatum flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats, at least in part, by modulating cardiac ET-1 and NF-kappaB signaling.
 ...
PMID:Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways. 1630 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>