• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.84-88
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• 2013

High risk of cardiovascular diseases caused by existing PPAR-${\gamma}$ agonists such as rosiglitazone and pioglitazone has been recently reported. CKD-501 is a novel selective PPAR-${\gamma}$ agonist as a potential target to reduce cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM). In this study, We investigated potential cardiotoxicity of CKD-501 and compared its toxicity with that of rosiglitazone or pioglitazone using db/db mice. After 12-week repeated administration of CKD-501 at doses of 3, 10 and 30 mg/kg/day or rosiglitazone at doses of 10 and 30 mg/kg/day or pioglitazone at doses of 200 and 540 mg/kg/day, animals were sacrificed for investigation of potential toxicities. Diameters of left ventricles and areas of cardiomyocytes were measured. And lipid accumulation and apoptosis in heart muscle were examined by oil red O staining and TUNEL staining, respectively. Diameters of left ventricles were significantly increased in high dose treatment group of pioglitazone compared to control (p<0.05), while other groups showed a tendency for an increase. All test articles induced significantly the increase of area of cardiomyocytes in heart compared to control (p<0.01), in regular order as pioglitazone > CKD-501 ${\geq}$ rosiglitazone. However, lipid accumulation and apoptotic changes in heart were not observed in all dosing groups. Taken together, the myocardial cell hypertrophy of CKD-501 are relatively lower than that of pioglitazone and similar to rosiglitazone. And it is suggested that the myocardial cell hypertrophy of CKD-501 are less adverse in clinical use for the management of the NIDDM.

• Journal of Pharmaceutical Investigation
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• v.40 no.6
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• pp.357-362
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• 2010

To enhance therapeutic effects of insulin-sensitizing adipokine, ADN gene and potent agonists, rosiglitazone for the $PPAR{\gamma}$, cationic liposomes as non-viral vectors were formulated. The particle size and zeta potential of drug loaded and unloaded cationic liposomes were investigated. The complex formation between cationic liposomes and negatively charged plasmid DNA was confirmed and the protection from DNase was observed. In vitro transfection was investigated in HepG2, HeLa, and HEK293 cells by mRNA expression of ADN. Encapsulation efficacy of rosiglitazone-loaded liposomes was determined by UV detection. Particle sizes of cationic liposomes were in the range of 110-170 nm and those of rosiglitazone-loaded cationic liposomes were in the range of 130-180 nm, respectively. Gel retardation of complexes indicated that the complex was formed at weight ratios of cationic lipid to plasmid DNA higher than 20:1. Both complexes protected plasmid DNA from DNase either drug free or drug loading. Encapsulation efficiency of rosiglitazone-loaded emulsion was increased by drug dose. The mRNA expression levels of ADN were dose-dependently increased in cells transfected with plasmid DNA. Therefore, cationic liposomes could be potential co-delivery system for drug and gene.

• Reproductive and Developmental Biology
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• v.37 no.4
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• pp.225-232
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• 2013

Satellite cells were derived from muscular tissue in postnatal pig. Satellite cell is an important to growth and development in animal tissues or organs. However, the progress underlying induced differentiation is not clear. The aim of this study was to evaluate the morphologic and the transcriptome changes in porcine satellite cell (PSC) treated with insulin, rosiglitazone, or dexamethasone respectively. PSC was obtained from postnatal muscle tissue. In study 1, for study the effect of insulin and FBS on the differentiated satellite cells, cells were cultured at absence or presence of insulin treated with FBS. Total RNA was extracted for determining the expression levels of myogenic PAX3, PAX7, Myf5, MyoD, and myogenin genes by real-time PCR. Myogenic genes decreased expression levels of mRNA in treated with insulin. In study 2, in order to clarify the relationship between rosiglitazone and lipid in differentiated satellite cells, we further examined the effect of FBS on lipid accumulation in the presence or absence of the rosiglitazone and lipid. Significant differences were observed between rosiglitazone and lipid by FBS. The mRNA of FABP4 and $PPAR{\gamma}$ increased in rosiglitazone treatment. In study 3, we examined the effect of dexamethasone on osteogenic differentiation in PSC. The mRNA was increased osteoblasotgenic ALP and ON genes treated with dexamethasone in 2% FBS. Dexamethasone induces osteoblastogenesis in differentiated PSC. Taken together, in differentiated PSCs, FABP4 and $PPAR{\gamma}$ increased to rosiglitazone. Whereas, no differences to FBS and lipid. These results were not comparable with previous reports. Our results suggest that adipogenic, myogenic, and osteoblastogenic could be isolated from porcine skeletal muscle, and identify culture conditions which optimize proliferation and differentiation formation of PSC.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.77-82
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• 2010

Peroxisome proliferator-activated receptor $\gamma$ (PPAR${\gamma}$) is a ligand-activated transcription factor that is used as a target for anti-diabetic drug development. In a search for novel PPAR${\gamma}$ agonists, the $\beta$-carboxyethyl-rhodanine derivative SP1818 was identified. We report here the characteristics of SP1818 as a selective PPAR${\gamma}$ agonist. In transactivation assays, SP1818 selectively activated PPAR${\gamma}$, but the degree of PPAR${\gamma}$ stimulation was less than with $1{\mu}M$ rosiglitazone. SP1818 also stimulated glucose uptake in a concentration-dependent manner. The adipocyte differentiation markers adiponectin, scavenger receptor CD36 and aP2 were weakly induced by treatment with SP1818, and TRAP220 subunit was specifically recruited into PPAR${\gamma}$ activated by rosiglitazone but not PPAR${\gamma}$ activated by SP1818.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.4
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• pp.181-186
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• 2006

This study was undertaken to evaluate whether peroxisome proliferator-activated-receptor-gamma $(PPAR-{\gamma})$ agonist-rosiglitazone (ROSI) induces postischemic functional recovery in Langendorf heart model. Hearts isolated from normal rats were subjected to 20 min of normoxia or 25 min zero-flow ischemia followed by 50 min reperfusion. In this acute protocol, ROSI $(20\;{\mu}g/ml)$ administered 10 min before ischemia had no effect on hemodynamic cardiac function, but had protective effect on lipid peroxidation in in vitro experiments. In chronic protocol in which ROSI was given by daily gavage (4 mg/kg) for three consecutive days, ROSI could not prevent the hemodynamic alteration on cardiac performance, but has protective effect on the activity of superoxide dismutase (SOD). There was no significant difference in the contents of reduced glutathione (GSH) and catalase activity between ischemia-reperfusion (IR) and ROSI treated IR hearts. Although ROSI had no effect on hemodynamic factor, it had effect on antioxidant activity. Our results indicate that ROSI provides partial beneficial effects by inhibiting lipid peroxidation and/or recovering normal level of SOD activity in the ischemic reperfused heart.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.99-105
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• 2012

Objectives : Korean red ginseng and Morus alba L. are used as a traditional treatment for diabetes. This study was designed to elucidate whether combination with Korean red ginseng and Morus alba L. (MPM) ameliorates metabolic syndrome in fructose-fed rats. Methods : Animals were divided into four groups; Control receiving tap water, fructose-fed, rosiglitazone-treated fructose-fed rats, and MPM-treated fructose-fed rats both receiving supplemented with 60% fructose (n=10). The MPM or rosiglitazone groups initially received a high-fructose (HF) diet alone for 8 weeks, with supplementation with MPM or rosiglitazone occurring during the final 6 weeks. Results : MPM and rosiglitazone, synthetic $PPAR{\gamma}$ agonist, treatment significantly prevented the increase in fasting serum glucose, leptin, triglyceride, and low density lipoprotein in the HF group when comparing with the control group. MPM and rosiglitazone also led to an increase in high density lipoprotein level in the HF group. The administration of MPM and rosiglitazone prevented the development of the metabolic disturbances such as impaired glucose tolerance, and blood pressure. MPM suppressed increased expressions of endothelin-1 (ET-1) in HF rat aorta. In addition, MPM significantly increased IR-${\beta}$ and PPAR-${\gamma}$ expression in muscle. Conclusions : Based on these results, we suggest that the administration of MPM improves metabolic syndrome through the alteration in lipid profiles and suppression of insulin resistant and blood pressure.

• Journal of Microbiology and Biotechnology
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• v.17 no.12
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• pp.1983-1990
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• 2007

Antidiabetic effects of a novel microbial biopolymer (PGB) 1 excreted from new Enterobacter sp. BL-2 were tested in the db/db mice. The animals were divided into normal control, rosiglitazone (0.005%, wt/wt), low PGB1 (0.1%, wt/wt), and high PGB1 (0.25%, wt/wt) groups. After 5 weeks, the blood glucose levels of high PGB1 and rosiglitazone supplemented groups were significantly lower than those of the control group. In hepatic glucose metabolic enzyme activities, the glucokinase activities of PGB1 supplemented groups were significantly higher than the control group, whereas the PEPCK activities were significantly lower. The plasma insulin and hepatic glycogen levels of the low and high PGB1 supplemented groups were significantly higher compared with the control group. Specifically, the insulin and glycogen increases were dose-responsive to PGB1 supplement. PGB1 supplement did not affect the IPGTT and IPITT compared with the control group; however, rosiglitazone significantly improved IPITT. High PGB1 and rosiglitazone supplementation preserved the appearance of islets and insulin-positive cells in immunohistochemical photographs of the pancreas compared with the control group. These results demonstrated that high PGB1 (0.25% in the diet) supplementation seemingly contributes to preventing the onset and progression of type 2 diabetes by stimulating insulin secretion and enhancing the hepatic glucose metabolic enzyme activities.

• Molecules and Cells
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• v.22 no.2
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• pp.239-245
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• 2006

This study examined whether adult bovine muscle satellite cells from 30-month-old Hanwoo cattle are multipotential. The satellite cells were found to have the potential to proliferate and differentiate into myoblasts with the formation of multinucleated cells. In addition, treatment with the peroxisome proliferator activating receptor-${\gamma}$ ($PPAR{\gamma}$) agonist, rosiglitazone, promoted their trans-differentiation into adipocytes with significant increases in glycerol accumulation and glycerol-3-phosphate dehydrogenase activity. Western blot analysis revealed that increased levels of the adipocyte fatty acid-binding protein, $PPAR{\gamma}$ and of CCAAT/enhancerbinding protein were closely related to rosiglitazoneinduced differentiation of the cells. These findings demonstrate that satellite cells from adult Hanwoo cattle are multipotent, and that their trans-differentiation into adipocytes can be induced by rosiglitazone.

• Journal of Veterinary Science
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• v.22 no.4
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• pp.53.1-53.13
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• 2021

Background: Canine adipose-derived stem cells (cADSCs) exhibit various differentiation properties and are isolated from the canine subcutaneous fat. Although cADSCs are valuable as tools for research on adipogenic differentiation, studies focusing on adipogenic differentiation methods and the underlying mechanisms are still lacking. Objectives: In this study, we aimed to establish an optimal method for adipogenic differentiation conditions of cADSCs and evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) and estrogen receptor (ER) signaling in the adipogenic differentiation. Methods: To induce adipogenic differentiation of cADSCs, 3 different adipogenic medium conditions, MDI, DRI, and MDRI, using 3-isobutyl-1-methylxanthine (M), dexamethasone (D), insulin (I), and rosiglitazone (R) were tested. Results: MDRI, addition of PPARγ agonist rosiglitazone to MDI, was the most significantly facilitated cADSC into adipocyte. GW9662, an antagonist of PPARγ, significantly reduced adipogenic differentiation induced by rosiglitazone. Adipogenic differentiation was also stimulated when 17β-estradiol was added to MDI and DRI, and this stimulation was inhibited by the ER antagonist ICI182,780. Conclusions: Taken together, our results suggest that PPARγ and ER signaling are related to the adipogenic differentiation of cADSCs. This study could provide basic information for future research on obesity or anti-obesity mechanisms in dogs.

• Polymer(Korea)
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• v.34 no.3
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• pp.274-281
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• 2010

In this study, PEG-PLA(or PLGA) amphiphilic di-block copolymers were synthesized by ring opening polymerization of D,L-lactide(or glycolide) and applied to polymeric micelle system for solubilization of a rosiglitazone as diabetes drug. The drug could be efficiently loaded into the polymer micelle by solid dispersion technique, and the drug-loaded micelles were characterized and evaluated as a drug delivery carrier by fluorescence spectrometer, DSC, and DLS measurements. The colloidal stability of drug loaded micelles in aqueous media could be enhanced by addition of 2-hydroxy-N-picolylnitinamide as a hydrotropic agent. The polymer micelles also showed biocompatible and nontoxic properties in vitro cell viability using MTT assay, and the drug loaded micelles were observed to be more effective than free drug for decreasing glucose in blood of rats.