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

The newly developed insulin sensitizer-thiazolidinediones have the potential to downregulate inflammation and autoimmune response. The objective of this study was to observe the beneficial effects on beta-cell function in the LADA patients treated with rosiglitazone. 54 LADA patients were assigned to oral hypoglycemic agents group (GAD-Ab<175 U/mL and FCP>0.3 nmol/L) or early insulin administration group (GAD-Ab>or=175 U/mL or GAD-Ab<175 U/mL and FCP<or=0.3 nmol/L). Then, those patients were randomly assigned to receive sulfonylureas (SUs group) or rosiglitazone (RSG group) therapy, or to receive insulin alone (INS group) or rosiglitazone plus insulin (INS+RSG group). Plasma glucose, HbA1c, fasting C-peptide (FCP) and C-peptide after 2h 75-g glucose load (PCP) were determined every 6 months. The levels of PCP and delta CP were higher in RSG group compared with those in SUs group after the 18th month. The PCP level (after the 12th month) and delta CP level (after the 18th month) in INS+/-RSG group were higher than those in INS group. Rosiglitazone combined with insulin wherever or not preserved beta-cell function in LADA patients after 3 years.
Diabetes Res Clin Pract 2009 Jan
PMID:Rosiglitazone preserves islet beta-cell function of adult-onset latent autoimmune diabetes in 3 years follow-up study. 1900 7

Thiazolidinediones (TZDs) are widely used in the type 2 diabetes mellitus (DMT2) treatment but have also been tested in cardiovascular prevention. DMT2 is associated with a marked increment in cardiovascular risk, and its prevention represents a main target in cardiometabolic protection. Both Troglitazone (Troglitazone in Prevention of Diabetes study) and Rosiglitazone (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication study) significantly reduced new-onset diabetes. A similar topic will be investigated with pioglitazone (Actos Now for Prevention of Diabetes). In the Prospective Pioglitazone Clinical Trial in Macrovascular events the primary end point (all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndromes, endovascular or surgical intervention in the coronary/leg arteries and amputation above ankles) was unaffected, whereas the secondary one (all-cause mortality, nonfatal myocardial infarction and stroke) was reduced by pioglitazone (-16%, p=0.027) compared to placebo in 5,238 patients with DMT2 and macrovascular disease. In contrast, a meta-analysis (Nissen and Wolski, N Engl J Med. 2007;356:2457-2471) reported that rosiglitazone treatment is associated with a significant increase in myocardial infarction risk (p=0.03) and a borderline significant increase in the risk of death from cardiovascular causes (p=0.06). Nevertheless, the possibility that rosiglitazone might affect cardiovascular events should be evaluated by the ongoing trial Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD). Interim findings early from RECORD did not show significant differences between the rosiglitazone and the control group regarding myocardial infarction and death from cardiovascular and any cause. Additional large-scale trials are awaited to clarify the of role TZDs in cardiovascular outcomes.
 ...
PMID:Cardiovascular risk and cardiometabolic protection: role of glitazones. 1903 66

Background. We investigated the level of soluble adhesion molecules in diabetic patients and the effect of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist rosiglitazone on plasma levels of adhesion molecules and an inflammation marker in type 2 diabetic patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Methods. A total of 116 diabetic patients with CAD who had undergone PCI were randomized to receive rosiglitazone (4 mg/d) or not for 6 months. Plasma levels of soluble intercellular adhesion molecules (sICAM-1) and P-selectin (sP-selectin) were measured on ELISA. Results. After 6-month rosiglitazone treatment, plasma levels of sICAM-1 were lower than baseline and control group levels (370.4 (332.4-421.9) pg/mL versus 423.5 (327.4-500.3) pg/mL and 404.6 (345.2-483.4) pg/mL, P < .001). In addition, plasma levels of C-reactive protein were significantly reduced from baseline levels. However, plasma level of sP-selectin was not significantly lowered with rosiglitazone treatment than with control treatment after 6-month follow-up. Conclusions. Rosiglitazone reduces chronic inflammatory responses and improves levels of markers of endothelial dysfunction in patients with diabetes and CAD. PPAR-gamma agonist may have a beneficial effect on the vascular endothelium through its anti-inflammatory mechanism and may be useful as therapy in patients undergoing PCI.
 ...
PMID:Antidiabetic rosiglitazone reduces soluble intercellular adhesion molecule-1 level in type 2 diabetic patients with coronary artery disease. 1910 16

The peroxisome proliferator-activated receptor (PPAR) gamma is one member of the nuclear receptor superfamily that contains in excess of 80 described receptors. PPARgamma activators are a diverse group of agents that range from endogenous fatty acids or derivatives (linolenic, linoleic, and 15-deoxy-Delta(12,14)-prostaglandin J(2)) to Food and Drug Administration-approved thiazolidinedione drugs [pioglitazone (Actos) and rosiglitazone (Avandia)] for the treatment of diabetes. Once activated, PPARgamma will preferentially bind with retinoid X receptor alpha and signal antiproliferative, antiangiogenic, and prodifferentiation pathways in several tissue types, thus making it a highly useful target for down-regulation of carcinogenesis. Although PPAR-gamma activators show many anticancer effects on cell lines, their advancement into human advanced cancer clinical trials has met with limited success. This article will review translational findings in PPARgamma activation and targeting in carcinogenesis prevention as they relate to the potential use of PPARgamma activators clinically as cancer chemoprevention strategies.
 ...
PMID:Peroxisome proliferator-activated receptor gamma pathway targeting in carcinogenesis: implications for chemoprevention. 1911 26

Thiazolidinediones are currently indicated for the treatment of Type 2 Diabetes. This class of drugs has been associated with several adverse reactions associated with volume overload. This report describes a case of a 65 year old African-American female with a history of hypertension and obesity, and taking rosiglitazone (Avandia) for her Type 2 Diabetes whose evaluation for chest pain resulted in the incidental finding of pulmonary hypertension noted on echocardiogram. The subsequent evaluation, follow-up and treatment are discussed along with potential pitfalls and implications for clinical care.
 ...
PMID:Thiazolidinedione associated volume overload and pulmonary hypertension. 1912 40

The nuclear hormone receptor, peroxisome proliferator-activated receptor (PPAR)-gamma, originally identified as a key mediator of adipogenesis, is expressed widely and implicated in diverse biological responses. Both natural and synthetic agonists of PPAR-gamma abrogated the stimulation of collagen synthesis and myofibroblast differentiation induced by transforming growth factor (TGF)-beta in vitro. To characterize the role of PPAR-gamma in the fibrotic process in vivo, the synthetic agonist rosiglitazone was used in a mouse model of scleroderma. Rosiglitazone attenuated bleomycin-induced skin inflammation and dermal fibrosis as well as subcutaneous lipoatrophy and counteracted the up-regulation of collagen gene expression and myofibroblast accumulation in the lesioned skin. Rosiglitazone treatment reduced the induction of the early-immediate transcription factor Egr-1 in situ without also blocking the activation of Smad2/3. In both explanted fibroblasts and skin organ cultures, rosiglitazone prevented the stimulation of collagen gene transcription and cell migration elicited by TGF-beta. Rosiglitazone-driven adipogenic differentiation of both fibroblasts and preadipocytes was abrogated in the presence of TGF-beta; this effect was accompanied by the concomitant down-regulation of cellular PPAR-gamma mRNA expression. Collectively, these results indicate that rosiglitazone treatment attenuates inflammation, dermal fibrosis, and subcutaneous lipoatrophy via PPAR-gamma in a mouse model of scleroderma and suggest that pharmacological PPAR-gamma ligands, widely used as insulin sensitizers in the treatment of type-2 diabetes mellitus, may be potential therapies for scleroderma.
 ...
PMID:Rosiglitazone abrogates bleomycin-induced scleroderma and blocks profibrotic responses through peroxisome proliferator-activated receptor-gamma. 1914 27

In this study, the effects of rosiglitazone on renal matrix metalloproteinase-9 (MMP-9) expression and its possible renoprotective mechanisms were investigated in streptozotocin-induced diabetic rats. We examined the urinary excretion rates of albumin (ALB), retinal-binding protein (RBP) and MMP-9 in control healthy rats (group C, n = 8), untreated diabetic rats (group D, n = 8) and diabetic rats treated with rosiglitazone (5mg/kg/day) (group R, n = 8) at eighth week. The renal tissue of diabetic rats was obtained for observing renal pathological changes by electron microscope and examining the expression of renal MMP-9 mRNA by RT-PCR. Our results showed that urinary excretion rates of MMP-9. ALB and RBP were significantly increased concurrently with the expression of renal MMP-9mRNA in group D compared with those of group C. Rosiglitazone significantly reduced urinary excretion rates of ALB, RBP and MMP-9 as well as the expression of renal MMP-9 mRNA. In addition, urinary excretion rate of MMP-9 showed positive relationship with urinary excretion rates of ALB and RBP. In conclusion, rosiglitazone definitely protects diabetic rats against renal injury, which may be partly associated with decreasing expression of renal MMP-9 mRNA and urinary MMP-9 production.
Diabetes Obes Metab 2009 May
PMID:Rosiglitazone protects diabetic rats against kidney injury through the suppression of renal matrix metalloproteinase-9 expression. 1923 38

ADOPT suggests that rosiglitazone, ahead of traditional therapies, can meet patient needs with respect to long-term glycaemic control, yet the recent safety debate, stimulated by retrospective meta-analysis, has seriously affected physician confidence to use it. Other recent evidence, including from a number of long-term outcome studies, does not confirm or exclude a cardiovascular risk signal for rosiglitazone, and evaluation of this data has led EMEA to support continued use of rosiglitazone, albeit with a recommendation not to use in patients with a previous cardiovascular history. Where does this leave us? Rosiglitazone remains the only oral blood glucose lowering agent to have demonstrated nearly 5 years of blood glucose control. Patients earlier in their disease, free of known cardiovascular disease, are just the patients to benefit most from long term glucose target achievement.
Prim Care Diabetes 2009 Feb
PMID:The new rosiglitazone story: its place today in type 2 diabetes management. 1928 41

Diabetes is an important health condition for the aging population; at least 20% of patients over the age of 65 years have diabetes, and this number can be expected to grow rapidly in the coming decades. Rosiglitazone, a drug in the thiazolidinedione class which targets insulin resistance, was approved by drug regulatory bodies based on its ability to improve glycemic control nearly ten years ago. The greatest long-term risk in diabetes is cardiovascular disease with macrovascular disease being the cause of as much as 80% of mortality. More recently the cardiovascular safety of rosiglitazone was brought to center stage following several meta-analyses and the unplanned interim analysis of the RECORD trial. As opposed to pioglitazone, current evidence points to rosiglitazone having a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas. A thiazolidinedione class effect however seems apparent with respect to the increased risk for fractures and congestive heart failure. Clinical trial evidence on rosiglitazone therapy in the elderly is limited. The available evidence is mainly related to observational cohort studies. Most of the trial evidence relates to a younger population and therefore these data can not be directly extrapolated to an older population. The effects of the thiazolidinedione drug class remain incompletely understood.
 ...
PMID:Safety and efficacy of rosiglitazone in the elderly diabetic patient. 1947 76

Rosiglitazone (RGZ), an oral anti-hyperglycemic agent used for non-insulin-dependent diabetes mellitus, is a high-affinity synthetic agonist for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Both in vitro and in vivo experiments have also revealed that RGZ possesses anti-inflammatory properties. Therefore, in the present study, we investigated the anti-inflammatory effects of RGZ in a rat model of periodontal disease induced by ligature placed around the mandible first molars of each animal. Male Wister rats were divided into four groups: 1) animals without ligature placement receiving administration of empty vehicle (control); 2) animals with ligature receiving administration of empty vehicle; 3) animals with ligature receiving administration with oral RGZ (10 mg/kg/day); and 4) animals with ligature receiving administration of subcutaneous RGZ (10 mg/kg/day). Thirty days after induction of periodontal disease, the animals were sacrificed, and mandibles and gingival tissues were removed for further analysis. An in vitro assay was also employed to test the inhibitory effects of RGZ on osteoclastogenesis. Histomorphological and immunohistochemical analyses of periodontal tissue demonstrated that RGZ-treated animals presented decreased bone resorption, along with reduced RANKL expression, compared to those animals with ligature, but treated with empty vehicle. Corresponding to such results obtained from in vivo experiments, RGZ also suppressed in vitro osteoclast differentiation in the presence of RANKL in MOCP-5 osteoclast precursor cells, along with the down-regulation of the expression of RANKL-induced TRAP mRNA. These data indicated that RGZ may suppress the bone resorption by inhibiting RANKL-mediated osteoclastogenesis elicited during the course of experimental periodontitis in rats.
 ...
PMID:PPAR-gamma agonist rosiglitazone prevents inflammatory periodontal bone loss by inhibiting osteoclastogenesis. 1950 2


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