• Clinical and Experimental Reproductive Medicine
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• 제32권4호
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• pp.347-352
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• 2005

Objective: The purpose of this study was to evaluate and compare the effects of metformin and rosiglitazone in overweight or obese women with polycystic ovarian syndrome. Methods: Twenty Six overweight or obese patients with polycystic ovarian syndrome were randomly treated with either metformin (500 mg three times daily, n=13) or rosiglitazone (4 mg once daily, n=13) for 6 months. Hormonal studies were performed before and after treatment. Insulin resistances were calculated by computerized HOMA 2 Calculator v2.2. Results: Testosterone decreased while SHBG increased after 6 months treatment in both metformin and rosiglitazone treatment groups. Fasting glucose decreased after metformin or rosiglitazone treatment. HOMA insulin resistance improved after treatment with either drug. There was no differences in hormonal changes and insulin resistance between 2 treatment groups. Conclusions: This study shows that metformin and rosiglitazone are effective in improving insulin sensitivity and ameliorating hyperandrogenism in overweight/obese polycystic ovarian syndrome women.

• The Korean Journal of Physiology and Pharmacology
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• 제26권2호
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• pp.135-144
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• 2022

An antidiabetic drug, rosiglitazone is a member of the drug class of thiazolidinedione. Although restrictions on use due to the possibility of heart toxicity have been removed, it is still a drug that is concerned about side effects on the heart. We here examined, using Chinese hamster ovary cells, the action of rosiglitazone on Kv1.5 channels, which is a major determinant of the duration of cardiac action potential. Rosiglitazone rapidly and reversibly inhibited Kv1.5 currents in a concentrationdependent manner (IC₅₀ = 18.9 μM) and accelerated the decay of Kv1.5 currents without modifying the activation kinetics. In addition, the deactivation of Kv1.5 current, assayed with tail current, was slowed by the drug. All of the results as well as the usedependence of the rosiglitazone-mediated blockade indicate that rosiglitazone acts on Kv1.5 channels as an open channel blocker. This study suggests that the cardiac side effects of rosiglitazone might be mediated in part by suppression of Kv1.5 channels, and therefore, raises a concern of using the drug for diabetic therapeutics.

• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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• pp.95-103
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• 2023

Rosiglitazone is a thiazolidinedione-class antidiabetic drug that reduces blood glucose and glycated hemoglobin levels. We here investigated the interaction of rosiglitazone with Kv3.1 expressed in Chinese hamster ovary cells using the wholecell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC₅₀ = 29.8 µM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazonemediated inhibition of Kv3.1 channels increased steeply in a sigmoidal pattern over the voltage range of -20 to +30 mV, whereas it was voltage-independent in the voltage range above +30 mV, where the channels were fully activated. The deactivation of Kv3.1 current, measured along with tail currents, was also slowed by the drug. In addition, the steady-state inactivation curve of Kv3.1 by rosiglitazone shifts to a negative potential without significant change in the slope value. All the results with the use dependence of the rosiglitazone-mediated blockade suggest that rosiglitazone acts on Kv3.1 channels as an open channel blocker.

• 한국식품영양과학회지
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• 제33권1호
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• pp.218-221
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• 2004

본 연구는 인술린비의존성 당뇨병환자의 경구용 혈당강하제로 사용되는 rosiglitazone이 in vivo 골조직 collagen의 신생율에 미치는 영향을 측정하기 위해 수행되었다. 저지방식이군과 고지방식이군은 각각 총열량의 10%와 45%를 지방으로 공급하였고 rosiglitazone 첨가군은 고지방식이에 rosiglitazone을 6.3 $\mu\textrm{g}$/kcal로 조절하여 공급하였다. 또한 collagen의 신생율을 안정동위원소비 질량분석법으로 측정하기 위하여 99.9% $^2$$H_2O$를 일시 복강주입하여 실험동물 체액의 $^2$$H_2O$ 수준을 2.0∼2.5%에 도달시킨 후 4% $^2$$H_2O$를 음용으로 3주 동안 계속 공급하였다. 체중증가량 및 식이섭취량은 각 실험군간에 유의한 차이가 없었으나 rosiglitazone첨가군이 다른 실험군에 비하여 높은 경향을 보였고, 체지방함량은 고지방식에 rosiglitazone를 첨가한 군이 다른 군에 비하여 유의한 증가를 보였다. 고지방식이군이 저지방식이군보다 골조직 collagen의 신생율이 낮았고 rosiglitazone의 첨가는 collagen의 신생율을 더욱 감소시켰으나 유의한 차이를 보이지는 않았다.

• 약학회지
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• 제53권6호
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• pp.357-367
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• 2009

A meta-analysis of 63 randomized controlled trials of Pioglitazone and Rosiglitazone in patients with type 2 diabetes was conducted. Pioglitazone significantly lowered fasting plasma glucose and triglyceride (TG) level and increased high-density lipoprotein cholesterol (HDL) level. Rosiglitazone significantly lowered hemoglobin A1C level and fasting plasma glucose, whereas it increased all kinds of lipids (HDL, LDL (low-density lipoprotein cholesterol), TG, total cholesterol). In comparison, glucose lowering effect was higher in Rosiglitazone, and Pioglitazone produced a more favorable lipid profile.

• 운동영양학회지
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• 제13권2호
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• pp.131-140
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• 2009

The aim of this study was to investigate the expression of PPAR-α, -β/δ, -γ, PGC-1α, GLUT-4 and p-AMPK-α₂ protein in the skeletal muscle of diabetic induced-rats by endurance training combined with rosiglitazone. The expression of PPAR-α, -β/δ, -γ, PGC-1α, GLUT-4 and p-AMPK-α₂ protein in red and white gastrocnemius by western blotting. The body weight was higher in diabetic induced-rats compared to the normal rats and after the treatment of exercise combined with rosiglitazone was significantly reduced in the all group. The levels of blood glucose was higher in diabetic induced-rats compared to the normal rats and after the treatment of exercise combined with rosiglitazone was significantly reduced in the all group. The expression of PPAR-α, -γ, PGC-1α in skeletal muscle of diabetic induced-rats were increased all groups and increased significantly in the group with exercise combined with rosiglitazone. The expression of GLUT-4 and p-AMPK-α₂ protein in the skeletal muscle of diabetic induced-rats were increased all groups and increased significantly in the group with exercise combined with rosiglitazoneI. These results suggest that exercise training and rosiglitazone may act as complementary therapies for the treatment of insulin rasistance.

• 약학회지
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• 제51권5호
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• pp.301-306
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• 2007

Rosiglitazone ($Avandia^{(R)}$) represents a new class of antidiabetic drugs which are $PPAR{\gamma}$ agonists. The present study was undertaken to determine whether the new antidiabetic rosiglitazone influences on the agonist-induced regulation of vascular smooth muscle contraction as an antihypertensive and, if so, to investigate the related mechanism. Endothelium-denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Rosiglitazone decreased Rho-kinase activating agonist (NaF or thromboxane $A_2$ mimetic)-induced contraction but not depolarization- or phorbol ester-induced contraction. Surprisingly, it slightly potentiated the latter contraction possibly opening a voltage-dependent calcium channel by its chemical structure on 50 mM KCI- or $1{\mu}M$ phorbol 12,13-dibutyrate-induced vasoconstriction. In conclusion, this study provides the evidence and possible related mechanism concerning the biphasic effect of an antidiabetic rosiglitazone as a possible antihypertensive on the agonistinduced contraction in rat aortic rings regardless of endothelial function.

• 분석과학
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• 제28권2호
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• pp.132-138
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• 2015

Rosiglitazone metabolites in rat plasma were analyzed after intraperitoneal and oral administration to rats. Seven metabolites (M1-M7) were detected in rat plasma (IP and PO), and the structures were confirmed using liquid chromatography-triple time of flight (TOF) mass spectrometry; as a result, the most abundant metabolite was M5, a de-methylated rosiglitazone. Other minor in vivo metabolites were driven from monooxygenation and demethylation (M2), thiazolidinedione ring-opening (M1, M3), mono-oxygenation (M4, M7), and mono-oxygenation followed by sulfation (M6). Among them, M1 was found to be a 3-{p-[2-(N-methyl-N-2-pyridylamino)ethoxy]phenyl}-2-(methylsulfinyl)propionamide, which is a novel metabolite of rosiglitazone. There was no significant difference in the metabolic profiles resulting from the two administrations. The findings of this study provide the first comparison of circulating metabolite profiles of rosiglitazone in rat after IP and PO administration and a novel metabolite of rosiglitazone in rat plasma.

• KSBB Journal
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• 제23권5호
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• pp.408-412
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• 2008

본 연구에서는 당뇨병치료제인 로시글리타존약물를 생분해성 PLGA 나노입자에 봉입시킴으로서 위장흡수율과 물에 대한 용해도를 증가시키기 위한 나노제제 개발에 기반을 두고 있다. 특히 제조조건에 따라 형태 및 크기가 조절가능한 나노입자를 제조하고자 하였고, 실험결과 Emulsion-evaporation방법을 사용하여 100-150 nm 크기의 고른 입자분포를 가진 나노입자를 제조하였다. 다양한 농도의 약물 존재하에서 나노입자를 제조함으로서 1%까지의 약물이 80% 이상의 봉입율로 제조될 수 있음을 확인하였다. 또한 나노입자의 크기는 PVA양을 조절하면서 크기분포를 제어하였다. 36시간 동안의 용출실험 결과 초기 약간의 Burst effect가 있었으나 36시간동안 일정하게 약물이 용출되어 나옴을 확인하였다. 앞으로의 연구를 통해, 고효율의 경구제제용 당뇨병치료제 운반체 개발에 중점을 둘 예정이다.

• Clinical and Experimental Pediatrics
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• 제56권4호
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• pp.151-158
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• 2013

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$, PPAR-${\gamma}$, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-${\gamma}$ agonist. Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-${\alpha}$, transforming growth factor (TGF)-${\beta}$, PPAR-${\alpha}$ and PPAR-${\gamma}$ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPAR${\alpha}$ and PPAR-${\gamma}$ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-${\alpha}$, and TGF-${\beta}$ mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-${\beta}$ expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. Conclusion: PPAR-${\alpha}$ and PPAR-${\gamma}$ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.