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논문분류	춘계학술대회 초록집
제목	Gemigliptin Improve Diabetic Nephropathy Independent of Glucose Control in db/db
저자	Jung-Woo Seo1, Yu-Ho Lee1, Se-Yun Kim1, Yang-Gyun Kim1, Kyung-Hwan Jeong1,Sang-Ho Lee1, Tae-Won Lee1, Chun-Gyoo Ihm1, Sung-Jig Ihm2, Ju-Young Moon1
출판정보	2014; 2014(1):
키워드	당뇨병성 신증, DPP-4 억제제, Akt pathway
초록	Background: Recent studies have reported that dipeptidyl peptidase (DPP) IV inhibitors reduced reactive oxygen species (ROS), podocyte apoptosis, and renal fibrosis in diabetes. However, the mechanism of DPP IV inhibitor in the development and progression of diabetic nephropathy remains not clear. In this study, we examined whether DPPIV inhibitor, gemigliptin, could attenuate diabetic nephropathy in a manner associated with regulation of Akt pathway in db/db mice. Methods: We designed four animal groups as following; 1) db/m; 2) db/db; 3) 0.04% gemigliptin- treated db/db (db/db+0.04% GG); 4) 0.4% gemigliptin-treated db/db (db/db+0.4% GG) from 8 to 20 weeks. Results: Dose-dependent gemigliptin treatment reduced kidney to body weight ratio, urinary albumin excretion, and mesangial expansion in db/db mice. Interestingly, db/db+0.04% GG showed similar physical and biochemical characteristics to that of db/db+0.4%, although HbA1c level remain unchanged in db/db+0.04% GG. Phosphorylated- Akt (p-Akt) was increased in db/db mice, however, 0.4% gemigliptin reduced p-Akt and modulated phosphorylated- FoxO3a (p-FoxO3a). 0.4% gemigliptin significantly attenuated the ratio of Bax/Bcl2 in db/db kidney. In addition, gemigliptin regulated iNOS and NAD(P)H oxidase (Nox4, p67-phox, p47-phox and p22-phox) in db/db kidney, resulting in the reduction of 8-OHdG production. Conclusion: Our study results indicated that gemigliptin modulate Akt/FoxO3a pathway in db/db kidney. It is resulted in decrease of microalbuminuria and glomerular injury without reduction of HbA1c. In addition, oxidative stress and apoptotic injury in diabetic kidney was attenuated by gemiglipin in a dose dependent manner. As taken together these results suggest that gemigliptin improve the tyep 2 diabetic nephropathy indepnednet of glucose control.
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