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)

This study was conducted to evaluate whether treatment of normal and diabetic rat hearts with rosiglitazone, a high-affinity ligand of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) used for the treatment of type 2 diabetes, improves postischemic functional recovery. The effects of acute rosiglitazone administration were investigated using working hearts isolated from normal rat or rats diabetic for 4 weeks after streptozotocin (STZ) injection. Hearts were subjected to 30 min of normothermic, zero-flow ischemia followed by 30-min reperfusion. Rosiglitazone (1 micromol/l) administered before ischemia had no effect on cardiac function during baseline perfusion, but it significantly improved aortic flow during reperfusion in both normal and diabetic hearts. In a chronic protocol in which rosiglitazone was given by daily gavage (10 micromol/kg body wt) immediately after STZ injection, rosiglitazone also prevented postischemic injury and significantly improved functional recovery. Using Western immunoblotting, it was demonstrated that the acute cardioprotective effect of rosiglitazone is associated with an inhibition of Jun NH(2)-terminal kinase phosphorylation in both normal and diabetic rat hearts. Furthermore, rosiglitazone also inhibited activating protein-1 DNA-binding activity. These data, demonstrating that rosiglitazone limits postischemic injury in isolated hearts, suggest an important function for PPAR-gamma in the heart.
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PMID:Rosiglitazone, a peroxisome proliferator-activated receptor-gamma, inhibits the Jun NH(2)-terminal kinase/activating protein 1 pathway and protects the heart from ischemia/reperfusion injury. 1197 49

Thiazolidinediones are a new class of drugs for the treatment of type 2 diabetes, and act by improving insulin sensitivity in adipose tissue, liver and skeletal muscle. Rosiglitazone and pioglitazone are registered for use in monotherapy, and in combination with sulfonylureas and metformin. Pioglitazone is also licensed for use in combination with insulin. There is level II evidence that in patients with inadequate glycaemic control both drugs reduce the level of HbA1c and fasting plasma glucose (FPG) when used as monotherapy and in combination with sulfonylurea or metformin or insulin; and both drugs increase levels of HDL and LDL and lower free fatty acid levels, but only pioglitazone significantly lowers triglyceride levels. Both drugs lower fasting insulin and C-peptide levels. In monotherapy, they may be slightly less potent at reducing the level of HbA1c than sulfonylureas or metformin. The maximal effect of these agents may not be seen for 6-14 weeks after commencement. Both drugs are well tolerated but liver function must be checked at baseline every second month for the first year, and periodically thereafter. The drugs are currently contraindicated in patients with moderate to severe liver dysfunction and alanine aminotransferase levels more than 2.5 times normal, New York Heart Association III-IV cardiac status, pregnancy, lactation and in children. The main side effects include weight gain, oedema, and mild dilutional anaemia.
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PMID:Thiazolidinediones and type 2 diabetes: new drugs for an old disease. 1204 35

Rosiglitazone (Avandia, Glaxo-SmithKline) belongs to a new family of oral hypoglycaemic agents, thiazolidinediones or glitazones. These molecules act as selective agonists of nuclear receptors (PPAR gamma) and improve insulin sensitivity. In Belgium as in all European countries, rosiglitazone is indicated for the treatment of type 2 diabetes, only in combination with another antidiabetic oral agent, in patients insufficiently controlled with metformin or a sulphonylurea at a maximal tolerated dose. In these patients, rosiglitazone, at a daily dose of 4 mg (sometimes 8 mg/day with metformin), reduces fasting glycaemia by 2-3 mmol/l and glycated haemoglobin level by about 1%. It exerts also favourable effects on some risk factors related to insulin resistance syndrome, which may contribute to improve cardiovascular prognosis of patients with type 2 diabetes. Hepatic safety of rosiglitazone seems to be good, although it is still recommended to check liver enzymes regularly. As all glitazones, rosiglitazone moderately promotes weight gain. It can also induce some fluid retention which may reveal or aggravate heart failure in at risk patients.
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PMID:[Medication of the month. Rosiglitazone (Avandia)]. 1207 98

Troglitazone maleate (Rezulin) has been associated with severe hepatotoxicity, which led to its withdrawal from the U.S. market in March 2000. Rosiglitazone maleate (Avandia) is being marketed as a safe alternative in the treatment of type 2 diabetes mellitus. We report a case of severe thiazolidinedione-induced cholestatic hepatitis in a 56-year-old female patient at a university hospital who was given rosiglitazone, 8 mg/day, after she developed milder hepatotoxicity while taking troglitazone. Rosiglitazone was discontinued, and the patient was treated with prednisone, azathioprine, and ursodiol. Clinical evaluation and liver biopsy were performed and liver function tests were monitored. After being switched from troglitazone to rosiglitazone the patient developed a severe cholestatic hepatitis with marked jaundice and moderate increases in serum alkaline phosphatase and gamma-glutamyltranspeptidase but only mild increases in serum aminotransferases. Discontinuation of rosiglitazone and treatment with prednisone, azathioprine, and ursodiol led to improvement, albeit with residual injury, dropout of intrahepatic bile ducts, and persisting elevations of serum alkaline phosphatase. Rosiglitazone is not always a safe alternative in patients who have had hepatotoxicity to troglitazone. It is important to monitor the serum alkaline phosphatase in addition to the serum aminotransferases in patients taking thiazolidinediones.
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PMID:Severe cholestatic hepatitis caused by thiazolidinediones: risks associated with substituting rosiglitazone for troglitazone. 1214 28

Rosiglitazone (CAS 155141-29-0, Avandia) is a novel insulin sensitizer used in the treatment of type 2 diabetes. A sensitive high performance liquid chromatography (HPLC) method for its determination in human plasma using fluorescence detection (excitation: 247 nm, emission: 367 nm) with a suitable internal standard (I. S.) is described. Ethyl acetate was used as extraction solvent. A mobile phase consisting of phosphate buffer, acetonitrile and methanol was used at a flow rate of 1.0 ml/min on a C18 column. The absolute recovery was > 90% and the lower limit of quantitation was 5 ng/ml. The intra- and inter-day relative standard deviations ranged from 0.58-6.69% and 0.82-6.63%, respectively. The method described is simple, economical, precise and accurate and has been successfully applied in a pharmacokinetic study conducted in healthy human volunteers.
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PMID:HPLC method for the determination of rosiglitazone in human plasma and its application in a clinical pharmacokinetic study. 1218 80

The pharmacokinetics and tolerability of a single 8-mg oral dose of rosiglitazone, an anti-diabetic agent, were compared in 10 long-term haemodialysis patients and 10 healthy volunteers. Haemodialysis patients received rosiglitazone 4 h after haemodialysis (non-dialysis day) and 3 h before haemodialysis (dialysis day). Haemodialysis did not influence rosiglitazone pharmacokinetics, and dialytic clearance was low (0.10 1/h). The mean area under the concentration-time curve (AUC(0-infinity)), the maximum observed plasma concentration (Cmax) and the half-life for rosiglitazone were similar in haemodialysis patients (non-dialysis day) and healthy individuals (2192 +/- 598 ng.h/ml versus 2388 +/- 494 ng.h/ml, 338 +/- 114 ng/ml versus 373 +/- 95 ng/ml, and 3.70 +/- 0.75 h versus 3.81 +/- 0.86 h, respectively). AUC(0-infinity) and Cmax were not markedly influenced by haemodialysis. Rosiglitazone dose adjustments are not warranted in patients with type 2 diabetes with end-stage renal failure on haemodialysis.
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PMID:Pharmacokinetics of rosiglitazone in patients with end-stage renal disease. 1223 21

The insulin sensitizer drug, rosiglitazone, has been shown to have a protective effect on pancreatic islet cell structure and function in animal models of type 2 diabetes. The identification of new molecular targets associated both with islet cell dysfunction and protection is a crucial research goal. In the present study, a proteomics approach has been used to identify such targets. Obese C57Bl/6J lep/lep mice and lean littermates were given the insulin sensitizer drug BRL49653, rosiglitazone. It normalized the impaired glucose tolerance in lep/lep mice but had no significant effect on glucose tolerance in the lean mice. Pancreatic islet polypeptides were arrayed by a two-dimensional gel electrophoresis system that separated more than 2500 individual spots. Three overexpressed and six underexpressed proteins were significant (p < 0.05) between lep/lep and lean mice, and four were modulated significantly (p < 0.05) by the rosiglitazone treatment of the obese mice. The identity of these differentially expressed proteins was made using mass spectrometric analysis and provided evidence that differential expression of actin-binding proteins may be an important aspect of defective islet function. Rosiglitazone increased carboxypeptidase B expression in both lep/lep and normal mice suggesting that this might be an independent effect of rosiglitazone that contributes to improved insulin processing.
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PMID:Effect of rosiglitazone on the differential expression of diabetes-associated proteins in pancreatic islets of C57Bl/6 lep/lep mice. 1223 79

The prevalence of type 2 diabetes increases dramatically with age in all populations. This report describes a post-hoc analysis of eight rosiglitazone monotherapy studies to characterise the efficacy and safety of rosiglitazone in older patients with type 2 diabetes, using a designation of > or = 70 years for elderly. A total of 3,127 patients were randomised to rosiglitazone (<70 years: n=2099; > or = 70 years: n = 427) or placebo (<70 years: n = 497; > or = 70 years: n=104). In both age groups, rosiglitazone 4 mg/day and 8 mg/day reduced HbA1c and fasting plasma glucose compared with baseline and placebo at week 26 with no difference between age groups. There was no difference between the nature, severity or type of adverse events experienced by older or younger patients. Rosiglitazone improves glycaemic control and is well tolerated in older as well as younger patients with type 2 diabetes.
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PMID:Rosiglitazone in the management of older patients with type 2 diabetes mellitus. 1229 17

Several drugs approved for a variety of indications have been shown to exhibit antiangiogenic effects. Our study focuses on the PPARgamma ligand rosiglitazone, a compound widely used in the treatment of type 2 diabetes. We demonstrate, for the first time to our knowledge, that PPARgamma is highly expressed in tumor endothelium and is activated by rosiglitazone in cultured endothelial cells. Furthermore, we show that rosiglitazone suppresses primary tumor growth and metastasis by both direct and indirect antiangiogenic effects. Rosiglitazone inhibits bovine capillary endothelial cell but not tumor cell proliferation at low doses in vitro and decreases VEGF production by tumor cells. In our in vivo studies, rosiglitazone suppresses angiogenesis in the chick chorioallantoic membrane, in the avascular cornea, and in a variety of primary tumors. These results suggest that PPARgamma ligands may be useful in treating angiogenic diseases such as cancer by inhibiting angiogenesis.
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PMID:PPARgamma ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. 1237 Feb 70

To compare the effects of rosiglitazone and pioglitazone on patient lipid levels in a clinical practice setting, we retrospectively examined charts of 20 patients in our practice. The patients had been treated for type 2 diabetes for 3 or more months with rosiglitazone (4 mg b.i.d.) followed immediately by 3 or more months' treatment with pioglitazone (45 mg once daily). Glycaemic control was excellent and essentially equivalent during the two treatments. At baseline, the mean HbA1c level was 7.6%; it dropped to 6.6% and 6.3% with rosiglitazone and pioglitazone treatment, respectively. Lipid levels, however, differed with the two treatments. Triglyceride levels rose 13% with rosiglitazone treatment, but fell 14% below baseline levels with pioglitazone therapy--a 24% reduction overall (p = 0.02). Rosiglitazone was associated with a significant increase in low-density lipoprotein cholesterol (LDL-C) levels (35%, p < 0.001 vs. baseline) and a significant increase in total cholesterol levels (22%, p < 0.001 vs. baseline). When pioglitazone replaced rosiglitazone therapy, LDL-C fell 25% (p < 0.001), and total cholesterol fell 19% (p < 0.001 between treatments). HDL-C levels did not change significantly during either treatment. Both drugs were otherwise safe and well tolerated. One patient receiving rosiglitazone and one receiving pioglitazone developed oedema that resolved without therapy discontinuation. Liver enzyme levels and blood pressure were unaffected in this group of patients. Because patients with diabetes are at risk for coronary artery disease, physicians should consider each agent's effects on lipid levels when choosing a specific thiazolidinedione.
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PMID:Differences in lipid profiles of patients given rosiglitazone followed by pioglitazone. 1244 84


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