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)

We have evaluated the possible association of polycystic ovary syndrome (PCOS) with 15 genomic variants previously described to influence insulin resistance, obesity, and/or type 2 diabetes mellitus. Seventy-two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase (three variants), plasma cell differentiation antigen glycoprotein, human sorbin and SH3 domain containing 1, plasminogen activator inhibitor-1, peroxisome proliferator-activated receptor-gamma2, protein tyrosine phosphatase 1B (two variants), adiponectin (two variants), IGF1, IGF2, IGF1 receptor, and IGF2 receptor. Compared with controls, PCOS patients were more frequently homozygous for the -108T variant in paraoxonase (36.6% vs. 9.5%; P = 0.002) and homozygous for G alleles of the ApaI variant in IGF2 (62.9% vs. 38.1%; P = 0.018). Paraoxonase is a serum antioxidant enzyme and, because -108T alleles result in decreased paraoxonase expression, this increase in oxidative stress might result in insulin resistance. G alleles of the ApaI variant in IGF2 may increase IGF2 expression, and IGF2 stimulates adrenal and ovarian androgen secretion. In conclusion, the paraoxonase -108 C-->T variant and the ApaI polymorphism in the IGF2 gene are associated with PCOS and might contribute to increased oxidative stress, insulin resistance, and hyperandrogenism in this prevalent disorder.
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PMID:Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. 1518 Oct 35

The study of protein and carbohydrate components of extracellular matrix in patients with alcoholic and non alcoholic steatohepatitis developed on the background of type 2 diabetes mellitus has shown a significant increase in collagen and glycosaminoglycan synthesis along with the enhancement of proteolytic and compensatory collagenous activity of blood plasma in patients with alcoholic steatohepatitis and inhibition of collagenolytic and proteolytic activity of blood plasma in patients with non alcoholic steatohepatitis against the background of diabetes mellitus, decrease in glycoprotein synthesis. Glutargin enhances metabolism of connective tissue by impeding collagen and glycosaminoglycan synthesis, activating proteoglycan production, augmenting blood plasma activity in patients with non alcoholic steatohepatitis, hindering proteolysis in patients with alcoholic steatohepatitis as well as increasing the excretion of connective tissue metabolites through urinary tracts.
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PMID:[Changes in indices of connective tissue in patients with alcoholic and non-alcoholic steatohepatitis and their correction with glutargin]. 1572 6

Circulating monocyte-platelet aggregates can release procoagulant, oxidative and mitogenic factors, thereby contributing to arterial thrombosis. The aim of our study was the estimation of heterophilic leukocyte-platelet aggregates in patients referred for coronary angiography, dependent on the degree of coronary stenosis and the disturbances of carbohydrate metabolism. Flow-cytometric analysis was performed in 50 consecutive patients with positive exercise test (age 54.2 +/- 6.4 years): 27 with normal glucose tolerance, 7 with impaired glucose tolerance and 16 with type 2 diabetes, and in 16 healthy subjects (age 44.8 +/- 14.1 years). We found that patients with coronary heart disease had increased leukocyte-platelet aggregate formation in comparison to the controls (the percentage of monocyte-platelet aggregates 47.5 +/- 23.0 vs 25.7 +/-12.8, p = 0.003, mean fluorescence intensity (MIF) 187.6 +/- 117.2 vs 79.3 +/- 42.8, p = 0.002, the percentage of granulocyte-platelet aggregates 20.7 +/- 10.4 vs 17.0 +/- 3.6, p = 0.009, MIF 64.2 +/- 41.3 vs 40.9 +/- 6.3, p = 0.008). The highest percentage of heterophilic aggregates was observed in patients with 1- and 2-vessel disease and those with "clean" vessels. In diabetic patients the percentage and MIF of granulocyte-platelet aggregates were decreased in comparison to the subjects with normal glucose tolerance (16.7 +/- 7.2 vs 22.8 +/- 9.8, p = 0.03 and 44.3 +/- 10.8 vs 74.4 +/- 48, p = 0.009, respectively). There was no increase in glycoprotein CD14 expression in any of the group studied. We found a positive correlation between the percentage of monocyte-platelet aggregates and fasting insulin level (r = 0.369, p = 0.04) and a negative correlation between MIF of monocyte-platelet aggregates and HDL level (r = -0.459, p = 0.012), between MIF CD14 and HDL level (r = -0.435, p = 0.02), and between the percentage of granulocyte-platelet aggregates and postprandial glycaemia (r = -0.4117, p = 0.03). We concluded that: 1. the patients with "clean" vessels represent a group of high atherothrombotic risk. 2. the patients with minimal coronary stenosis may benefit from anti-inflammatory and antiplatelet treatment.
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PMID:[Platelet-monocyte aggregate formation in patients with coronary heart disease and disorders of carbohydrate metabolism]. 1572 88

Anticardiolipin and anti-beta2 glycoprotein I antibodies are associated with an increased tendency to thrombosis by various mechanisms. This study aimed to evaluate the association between micro and macrovascular complications of diabetes and anticardiolipin and anti-beta2 glycoprotein I antibodies. Forty-six patients with type 2 diabetes mellitus (T2DM) were studied. Twenty-one patients had coronary artery disease as a macrovascular complication. Twenty-five age and sex matched healthy subjects formed a control group. Anticardiolipin IgM, IgG, anti-beta2 glycoprotein IgM and IgG antibody levels were studied in both patient and control groups. Diabetic patients with ischaemic heart disease had significantly higher titres of anticardiolipin IgG antibody than patients without ischaemic heart disease (P < 0.001). However, none of these patients had an anticardiolipin IgG antibody level higher than 20 GPL, which is accepted as a clinically significant value, so this association may not be clinically important. There was no association with the microvascular complications. There was also no significant association between anti-beta2 glycoprotein I antibodies in type 2 diabetic patients and micro and macrovascular complications. Anticardiolipin and anti-beta2 glycoprotein I antibodies do not have a major role in the pathogenesis of diabetic complications in type 2 diabetic patients. Prospective studies of large populations are needed to explore this association further.
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PMID:Anticardiolipin and anti-beta2 glycoprotein I antibody concentrations in patients with type 2 diabetes mellitus. 1593 58

alpha2-Heremans-Schmid glycoprotein (AHSG) is an abundant plasma protein synthesized predominantly in the liver. The AHSG gene, consisting of seven exons and spanning 8.2 kb of genomic DNA, is located at chromosome 3q27, a susceptibility locus for type 2 diabetes and the metabolic syndrome. AHSG is a natural inhibitor of the insulin receptor tyrosine kinase, and AHSG-null mice exhibit significantly enhanced insulin sensitivity. These observations suggested that the AHSG gene is a strong positional and biological candidate for type 2 diabetes susceptibility. Direct sequencing of the AHSG promoter region and exons identified nine common single nucleotide polymorphisms (SNPs) with a minor allele frequency > or =5%. We carried out a detailed genetic association study of the contribution of these common AHSG SNPs to genetic susceptibility of type 2 diabetes in French Caucasians. The major allele of a synonymous coding SNP in exon 7 (rs1071592) presented significant evidence of association with type 2 diabetes (P = 0.008, odds ratio 1.27 [95% CI 1.06-1.52]). Two other SNPs (rs2248690 and rs4918) in strong linkage disequilibrium with rs1071592 showed evidence approaching significance. A haplotype carrying the minor allele of SNP rs1071592 was protective against type 2 diabetes (P = 0.014). However, our analyses indicated that rs1071592 is not associated with the evidence for linkage of type 2 diabetes to 3q27.
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PMID:A synonymous coding polymorphism in the alpha2-Heremans-schmid glycoprotein gene is associated with type 2 diabetes in French Caucasians. 1604 17

Pancreatic beta cell-surface expression of glucose transporter 2 (Glut-2) is essential for glucose-stimulated insulin secretion, thereby controlling blood glucose homeostasis in response to dietary intake. We show that the murine GlcNAcT-IVa glycosyltransferase is required for Glut-2 residency on the beta cell surface by constructing a cell-type- and glycoprotein-specific N-glycan ligand for pancreatic lectin receptors. Loss of GlcNAcT-IVa, or the addition of glycan-ligand mimetics, attenuates Glut-2 cell-surface half-life, provoking endocytosis with redistribution into endosomes and lysosomes. The ensuing impairment of glucose-stimulated insulin secretion leads to metabolic dysfunction diagnostic of type 2 diabetes. Remarkably, the induction of diabetes by chronic ingestion of a high-fat diet is associated with reduced GlcNAcT-IV expression and attenuated Glut-2 glycosylation coincident with Glut-2 endocytosis. We infer that beta cell glucose-transporter glycosylation mediates a link between diet and insulin production that typically suppresses the pathogenesis of type 2 diabetes.
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PMID:Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes. 1637 70

Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect of MSE could be due to its predominant effect on mucosal glycoprotein, cell proliferation, free radicals and antioxidant systems.
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PMID:Effect of plantain banana on gastric ulceration in NIDDM rats: role of gastric mucosal glycoproteins, cell proliferation, antioxidants and free radicals. 1662 71

Rosiglitazone is one of the members in the thiazolidinedione (TZD) class of anti-diabetic agents that have proven efficacy in the treatment of patients with type 2 diabetes. We studied serum from a patient who developed acute, severe thrombocytopenia after exposure to rosiglitazone maleate (Avandia) and proposed the mechanisms for rosiglitazone-induced thrombocytopenia. Tested by flow cytometry, the patient's serum was positive for rosiglitazone-induced antibody with the binding ratio of 5.93 (mean fluorescence intensity, MFI) in the presence of the patient's serum and rosiglitazone in a final concentration of 0.53 mmol/l. The antibody was found to bind both glycoprotein (GP) IIb-IIIa complex and GP Ib/IX complex by MAIPA assay using five different monoclonal antibodies (mAbs) against GP complexes Ib/IX, GPIIb/IIIa or GPIa/IIa. Immunoprecipitation studies showed that both GPIIb/IIIa and GP Ib/IX complex were precipitated by antibody in the presence, but not in the absence of rosiglitazone. These findings provide evidence that immune thrombocytopenia can be caused by sensitivity to the antidiabetic agent rosiglitazone maleate. This report documents the first case of rosiglitazone-induced immune thrombocytopenia.
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PMID:Rosiglitazone-induced immune thrombocytopenia. 1712 88

A direct consequence of increased platelet sensitivity in diabetes mellitus might be augmented release of platelet granule contents, which, in turn, may lead to the formation of a platelet volume gradient, increased platelet turnover and reduced survival of platelets from diabetic individuals. In this study we addressed the question whether diabetes-induced and lipid fluidity-mediated changes in platelet receptor exposure and accessibility might be part of a general mechanism underlying the increased rate of platelet ageing and reduced platelet survival in diabetes. Diabetic individuals showed higher numbers of platelets of extreme dimensions: very small platelets and larger platelets were more frequent compared to controls ( P(chi(2))< 0.03). The shifts in platelet volume distributions were paralleled by decreased expression of the alpha subunit of glycoprotein Ib (by up to 17%, P < 0.01) in platelet membranes from diabetic patients, increased expression of P-selectin in thrombin-stimulated diabetic platelets (P< 0.02), an increased number of platelet microparticles in diabetic individuals (P< 0.05 or P< 0.03 for resting or stimulated platelets, respectively), and reduced platelet membrane fluidity (by 5.2 +/- 0.6%, P< 0.01). We suggest that the distinct bimodality of platelet distribution in diabetic patients might arise from accelerated thrombopoiesis in diabetic subjects, and this is supported by the demonstration of elevated fractions of reticulated (rich with residual RNA) platelets in diabetic patients (14.6 +/- 5.6% vs 8.1 + 2.1% p(u) < 0.025). Overall, our results point to a fluidity-mediated platelet hypersensitivity and accelerated rate of platelet production in subjects with type 2 diabetes mellitus, which results in a greater number of very large and hypersensitive younger platelets and a more abundant fraction of small exhausted platelets.
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PMID:Possible mechanisms of the altered platelet volume distribution in type 2 diabetes: does increased platelet activation contribute to platelet size heterogeneity? 1680 Oct 71

Pre-eclampsia (P-Ec) is a complex multisystem disorder of unknown aetiology reported to occur in about 6% to 8% of all pregnancies throughout the world. This disease is associated with fibrin deposition and occlusive lesions in placental vessels. Pro-thrombin activatable fibrinolysis inhibitor (pro-TAFI) is a relatively recently described glycoprotein that can be converted into its active form (TAFIa) by thrombin, thrombin-thrombomodulin and plasmin. TAFIa potentially inhibits fibrinolysis by removing C-terminal lysine and arginine residues from fibrin. These residues are required for adsorption of tissue-type plasminogen activator (t-PA) and plasminogen to fibrin. Therefore, TAFIa decreases plasmin formation and protects the fibrin clot against lysis. An increased of pro-TAFI/TAFIa levels has been reported in some clinical conditions associated with thrombotic tendency, as type II diabetes mellitus, deep vein thrombosis and symptomatic artery disease. Few studies have investigated pro-TAFI/TAFIa in normal or complicated pregnancy but contrasting results were reported. Understanding the role of pro-TAFI/TAFIa in the pathogenesis of P-Ec can hold great promise for improving P-Ec management. In this context, a large-scale study evaluating plasma TAFI antigen and activity, its synthesis and metabolism in pre-eclamptic women is required. Recently new selective TAFIa inhibitors have been developed. The design of a new therapy to treat and/or prevent P-Ec, based on successful use of TAFIa inhibitors, may have significant clinical ramifications.
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PMID:Thrombin activatable fibrinolysis inhibitor (TAFI): a role in pre-eclampsia? 1718 58


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