Inhibition of 11β-Hydroxysteroid Dehydrogenase Improves Glucose Metabolism in Insulin Resistant Otsuka Long-Evans Tokushima Fatty Rats
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概要
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Increased activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) has been implicated in the development of the metabolic syndromes by amplification of local glucocorticoid actions through regeneration of active glucocorticoid receptor. The present study was examined whether inhibition of 11β-HSD-1 by carbenoxolone (CBX), a non-selective 11β-HSD inhibitor, improved carbohydrate metabolism in insulin resistant Otsuka Long-Evans Tokushima Fatty (OLETF) rats or not. Rats received subcutaneous CBX, twice a day [50 mg/kg bodyweight (b.w.)] or vehicle for 2 weeks, and then were evaluated fasting blood glucose levels, glucose tolerance, serum fasting insulin levels, and blood lipid levels in the both groups. The fasting blood glucose and insulin were lower in CBX-treated OLETF rats at 2 weeks than those of compared to day 0 and vehicle-treated OLETF rats at 2 weeks. Blood glucose fluctuations of the CBX-treated OLETF rats were more normal than those of vehicle-treated ones during intraperitoneal glucose tolerance tests. Blood concentrations of cholesterol and free fatty acids in the CBX-treated OLETF rats were lesser than those of vehicle-treated ones. The area under time-concentration curve (AUC120 min) of blood glucose during the glucose tolerance test and of CBX-treated OLETF rats was significantly lower than that of the vehicle-treated ones, and insulinogenic index (ISI30 min) was significantly different between CBX-and vehicle-treated groups. These results suggested that inhibition of 11β-HSD-1 by CBX might be improved carbohydrate metabolism and lipid profile in the insulin-resistant OLETF rats.
- 公益社団法人 日本薬学会の論文
著者
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Kim Young-Hoon
Division of Cardiology, Cardiovascular Center
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KIM Dong-Sun
Department of DxB Communication Convergence Research Center, Korea Electronics Technology Institute
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Kim Dong-sun
Department Of Civil And Ocean Engineering Ehime University
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Kim Young-hoon
Division Of Cardiology Cardiovascular Center
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Park Yoo-Sin
Department of Pharmacology and Clinical Pharmacology Lab, College of Medicinee, Hanyang University
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Kim Shin-Hee
Department of Pharmacology and Clinical Pharmacology Lab, College of Medicinee, Hanyang University
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Jhee Ok-Hwa
Department of Practical Arts Education, Gongju National University of Education
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Lee Seong-Jin
Department of Internal Medicine, College of Medicine, Hallym University Sacred Heart Hospital
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Kim Tae-Wha
Department of Internal Medicine, College of Medicine, Hanyang University
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Kang Ju-Seop
Department of Pharmacology and Clinical Pharmacology Lab, College of Medicinee, Hanyang University
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Jhee Ok-hwa
Department Of Practical Arts Education Gongju National University Of Education
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Kang Ju-seop
Department Of Pharmacology & Institute Of Biomedical Sciences College Of Medicine : Department O
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Park Yoon-Sin
Department of Pharmacology and Clinical Pharmacology Lab, College of Medicinee, Hanyang University
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KIM Shin-Hee
Department of Pharmacology & Institute of Biomedical Sciences, College of Medicine ; Department of Bioengineering, Hanyang University
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Kim Dong-Sun
Department of Internal Medicine, College of Medicine, Hanyang University
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Kim Young-Hoon
Division of Molecular Therapeutics Development, Hanyang Biomedical Research Institutee, Hanyang University
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