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J.Health Sci., 57(4), 378-383, 2011
-Rapid Communication-
Inhibition of 11β-Hydroxysteroid Dehydrogenase Improves Glucose Metabolism in Insulin Resistant Otsuka Long-Evans Tokushima Fatty Rats
Dong-Sun Kim,a Yoo-Sin Park,b, c
Shin-Hee Kim,b, c Young-Hoon Kim,c, d
Ok-Hwa Jhee,e Seong-Jin Lee,f
Tae-Wha Kim,a and Ju-Seop Kang*, b, c
aDepartment of Internal Medicine, College of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea,
bDepartment of Pharmacology and Clinical Pharmacology Lab, College of Medicine,
cDivision of Molecular Therapeutics Development, Hanyang Biomedical Research Institute and
dDepartment of Medicine, Graduate School of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea,
eDepartment of Practical Arts Education, Gongju National University of Education, 376 Bonghwang-dong, Gongju 314-711, Republic of Korea and
fDepartment of Internal Medicine, College of Medicine, Hallym University Sacred Heart Hospital, 896 Pyeongchon-dong, Dongan-gu, Anyangsi 431-070, Republic of Korea
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.
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