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논문분류	춘계학술대회 초록집
제목	Effects of Dipeptidyl Peptidase IV Inhibition on Renal Function in Type 2 Diabetic Mice
저자	Ji Eun Lee1, Jung Eun Kim2, Mi Hwa Lee2, Hye Kyoung Song2, Jung Yeon Ghee2,Hyunwook Kim1, Jin Joo Cha2, Hye Sook Min2, Sung Jin Kim2, Sang Yeob Han3,Mi Jin Lee2, Young Sun Kang2, Jee Young Han4, Dae Ryong Cha2
출판정보	2014; 2014(1):
키워드	DPPIV, 당뇨병성신증, 족세포
초록	Purpose: The aim of the present study is to investigate the mechanism and effect of dipeptidyl peptidase (DPP) IV inhibition on renal injury in db/db mice. Methods: The mice were divided into three groups as follows: non-diabetic db/m mice, untreated db/db mice, and db/db mice treated with DA-1229 (300mg/kg/d) for 12 weeks. Results: There were no difference in liver, fat and heart DPP4 activities and active GLP-1 levels between db/m mice and db/db mice, and these activities were suppressed by DA-1229 in db/db mice. Although plasma DPPIV activity did not show significant differences among groups, DPPIV activity in kidney was significantly higher in diabetic mice compared with control db/m mice, which was abolished by DPPIV inhibition. DPPIV treatment induced significant improvement in lipid abnormality and hepatic steatosis. However, there was no significant change in HbA1c and HOMA-IR after DPPIV inhibition. Treatment with DA-1229 for 12 weeks showed a little effect on body weight, systolic blood pressure and insulin resistance. DA-1229 treatment improved renal lipid metabolism, renal hypertrophy and significantly decreased urinary albumin excretion and fibrotic process in the kidney. Moreover, treatment with DA- 1229 induced a significant reduction in serum creatinine and improvement in creatinine clearance in db/db mice. Interestingly, DA-1229 treatment significantly decreased urinary excretion of nephrin, and high glucose and angiotensin II stimulation significantly increased DPPIV activity in cultured podocytes. Conclusion: A novel DPPIV inhibitor, DA-1229 improved lipid abnormality and ameliorated renal injury in db/db mice independent of glucose lowering effect. Our data suggest that renoprotective effects of DA-1229 in db/db mice may be associated with suppression of kidney DPPIV activity irrespective of insulin resistance and possibly mediated by improvement of podocyte injury.
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