Disease relevance of Rosiglitazone maleate

• Circulating resistin levels are decreased by the anti-diabetic drug rosiglitazone, and increased in diet-induced and genetic forms of obesity [1].
• Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial [2].
• Dose-dependent increases in body weight and total and low-density lipoprotein cholesterol levels were observed (P<.001 for both rosiglitazone groups vs placebo) [2].
• INTERVENTION: Rosiglitazone (4 mg/d for 4 weeks and then 4 mg twice daily for 8 weeks), an insulin-sensitizing agent, was given to 7 insulin-resistant subjects with hypertension [3].
• PPAR-gamma activating thiazolidinediones (TZDs) rosiglitazone and troglitazone induced G(0)-G(1) cell-cycle arrest and apoptosis in human, rat somatolactotroph, and murine gonadotroph pituitary tumor cells, and suppressed in vitro hormone secretion [4].
• This randomized, placebo-controlled trial did not show benefit of 4 mg/day of rosiglitazone on lipoatrophy or metabolic parameters in patients with HIV lipodystrophy [5].
• We selectively confirmed rosiglitazone-mediated effects on expression of key regulators of breast cancer proliferation and apoptosis, including p53, p21 and Bax [6].
• Rosiglitazone treatment increased liver steatosis, particularly microvesicular steatosis [7].
• Rosi treatment did not affect hyperglycemia but did reduce oxidative stress and prevented the development of thermal hypoalgesia [8].
• Rosiglitazone reduced the parasitemia in a CD36-dependent manner in the Plasmodium chabaudi chabaudi hyperparasitemia model [9].

Psychiatry related information on Rosiglitazone maleate

• However, the mechanisms underlying the potential beneficial effects of rosiglitazone in Alzheimer's disease remain unclear [10].
• Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice [10].
• A time-response study was performed with 1 mg/kg/day rosiglitazone (the minimum dose found to significantly affect adhesion formation) [11].
• METHODS: We report our experience with a low-calorie diet (800 cal, sodium content 1500 mmol/day) combined with behavior modification on eight patients treated with thiazolidinediones (six pioglitazone and two rosiglitazone) [12].
• We report here our studies on troglitazone and rosiglitazone cytotoxicity in human hepatocytes isolated from multiple donors to investigate factors responsible for individual differences in sensitivity to the known hepatotoxicity of these antidiabetic drugs [13].

High impact information on Rosiglitazone maleate

• Development of murine corticotroph tumors, generated by subcutaneous injection of ACTH-secreting AtT20 cells, was prevented in four of five mice treated with the thiazolidinedione compound rosiglitazone, and ACTH and corticosterone secretion was suppressed in all treated mice [14].
• This effect is completely inhibited by the peroxisome proliferator-activated receptor (PPAR)gamma antagonist GW9662 and mimicked by PPARgamma agonists Rosiglitazone and 1-O-hexadecyl-2-azeleoyl-phosphatidylcholine [15].
• Their study in mice reveals that treatment with the thiazolidinedione rosiglitazone or exposure to a high-fat diet promotes the trafficking of circulating bone marrow-derived progenitor cells into adipose tissue, where they become multilocular adipocytes [16].
• Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone [17].
• These data reveal mitochondrial remodeling and increased energy expenditure in white fat in response to rosiglitazone treatment in vivo and suggest that enhanced lipid utilization in this tissue may affect whole-body energy homeostasis and insulin sensitivity [17].

Chemical compound and disease context of Rosiglitazone maleate

• Glucose uptake during ischemia was also normalized by rosiglitazone treatment, thereby preventing the greater loss of ATP and restoring recovery of contractile function to that of lean rat hearts [18].
• We tested the effects of the thiazolidinedione rosiglitazone on blood pressure and endothelial function in insulin-resistant fatty Zucker rats, which display hypertension and abnormal endothelial cell function [19].
• Fenofibrate treatment decreased body weight and visceral fat, whereas rosiglitazone treatment increased body weight [20].
• Treatment of Spontaneously Hypertensive Rats With Rosiglitazone and/or Enalapril Restores Balance Between Vasodilator and Vasoconstrictor Actions of Insulin With Simultaneous Improvement in Hypertension and Insulin Resistance [21].
• Treatment of SHRs with rosiglitazone (insulin sensitizer) and/or enalapril (ACE inhibitor) may simultaneously improve hypertension, insulin resistance, and endothelial dysfunction by rebalancing insulin-stimulated production of vasoactive mediators [21].

Biological context of Rosiglitazone maleate

• Rosiglitazone inhibits bovine capillary endothelial cell but not tumor cell proliferation at low doses in vitro and decreases VEGF production by tumor cells [22].
• Functionally, adipocytes from rosiglitazone-treated mice displayed markedly enhanced oxygen consumption and significantly increased palmitate oxidation [17].
• We found that mice with CD knockout of this receptor were resistant to the rosiglitazone- (RGZ) induced increases in body weight and plasma volume expansion found in control mice expressing PPARgamma in the CD [23].
• Rosiglitazone seemed to ameliorate insulin resistance judged by the decreased serum insulin concentrations and % liver fat [24].
• Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone [25].

Anatomical context of Rosiglitazone maleate

• Rosiglitazone changes the morphological features and protein profiles of mitochondria in 3T3-L1 adipocytes [17].
• Agents that enhance insulin sensitivity, such as rosiglitazone, appear to exert their therapeutic effect through adipose tissue, but the precise mechanisms of their actions are unclear [17].
• 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 [22].
• In our in vivo studies, rosiglitazone suppresses angiogenesis in the chick chorioallantoic membrane, in the avascular cornea, and in a variety of primary tumors [22].
• PATIENT: 69-year-old man taking rosiglitazone, 4 mg/d. INTERVENTION: Discontinuation of rosiglitazone therapy and treatment with lactulose, vitamin K, fresh frozen plasma, ventilatory assistance, and intensive care unit support [26].

Associations of Rosiglitazone maleate with other chemical compounds

• Natural and synthetic PPARgamma agonists, including the thiazolidinedione rosiglitazone (Ro), modestly induced the expression of a surprisingly small number of genes, several of which were also induced by a specific PPARdelta agonist [27].
• Treatment of cells with 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2)) inhibited the LPS- and IFN-gamma-dependent synthesis of NO, a process that was not antagonized by similar concentrations of prostaglandin J(2), prostaglandin E(2), or rosiglitazone, a peroxisomal proliferator-activated receptor gamma ligand [28].
• During differentiation of trophoblast stem cells, PPARgamma is strongly induced, and Muc1 expression is upregulated by the PPARgamma agonist rosiglitazone [29].
• The PPARgamma inhibitor T0070907 was significantly more efficient at causing cancer cell death than the activators troglitazone and rosiglitazone [30].
• In homogenates of skeletal muscle, metformin and TZDs reduced the activity of complex I (30 mmol/l metformin, -15 +/- 2%; 100 micromol/l rosiglitazone, -54 +/- 7; and 100 micromol/l pioglitazone, -12 +/- 4; P < 0.05 each) [31].
• Rosiglitazone, but not metformin, increased adiponectin but also increased LDL-cholesterol and decreased HDL-cholesterol [32].
• Changes in bone-specific ALP levels showed a moderate negative correlation with the changes in the TNF-alpha levels after rosiglitazone treatment and after diet in the diabetic control group [33].
• Rosiglitazone mitigates the increase in FFA after infusion of triglyceride/heparin and prevents FFA-induced endothelial dysfunction [34].

Gene context of Rosiglitazone maleate

• We report here that the PPARgamma-specific agonists rosiglitazone and GW7845 strongly inhibited the development of atherosclerosis in LDL receptor-deficient male mice, despite increased expression of the CD36 scavenger receptor in the arterial wall [35].
• We used the PPAR agonist rosiglitazone (Rtz) to investigate PPAR-gamma isotype on IL-1beta-target genes [36].
• Using an experimental murine model of LC migration induced by TNF-alpha, we show that the highly potent PPAR gamma agonist rosiglitazone specifically impairs the departure of LCs from the epidermis [37].
• Here, we show that the activation of PPARgamma by its selective ligand, rosiglitazone, upregulates PTEN expression in human macrophages, Caco2 colorectal cancer cells, and MCF7 breast cancer cells [38].
• In conclusion, the insulin-sensitizing effects of rosiglitazone are independent of enhanced signaling of IRS-1/PI 3-kinase/Akt/AS160 in patients with newly diagnosed type 2 diabetes [39].
• The GR agonist dexamethasone synergised with rosiglitazone to stimulate the ADIPOR2 promoter wheras the GR antagonist RU486 abolished this stimulation [40].
• Rosiglitazone stimulated an increase in the ADP/ATP ratio in endothelial cells, and LKB1 was essential for rosiglitazone-stimulated AMPK activity in HeLa cells [41].
• Improved blastocyst quality in obese females treated with rosiglitazone before mating indicates that peroxisome proliferator activated receptor-gamma is a key target for metabolic regulation of ovarian function and oocyte quality [42].

Analytical, diagnostic and therapeutic context of Rosiglitazone maleate

• About half of those genes were upregulated after treatment with rosiglitazone, and this was accompanied by an increase in mitochondrial mass and changes in mitochondrial structure [17].
• However, rosiglitazone decreased % liver fat (spectroscopy) and serum insulin concentrations, and normalized liver function tests [24].
• We report here that oral administration of thiazolidinediones (rosiglitazone and troglitazone) remarkably inhibited insulin-like growth factor-I (IGF-I)-promoted skin tumor development by 73% in BK5.IGF-1 transgenic mice, although they were previously found to be ineffective in inhibiting UV- or chemically induced mouse skin tumorigenesis [43].
• To determine the specific effects of rosiglitazone (RSG) on beta-cell mass dynamics, male fa/fa (obese) and +/fa or +/+ (lean) rats age 6 weeks were fed either chow (control group [CN]) or chow mixed with rosiglitazone (RSG group) at a dosage of 10 micromol. kg(-1) body wt.day(-1) [44].
• The present study examines the effect of rosiglitazone treatment on cardiac insulin sensitization and its association with cardioprotection from ischemia/reperfusion injury in an animal model of diabetes [45].

References