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Anti-obesity effects of KR-66195, a synthetic DPP-IV inhibitor, in diet-induced obese mice and obese-diabetic ob/ob mice

Authors
 Eun Young Lee  ;  Yeon Wook Kim  ;  Hyunhee Oh  ;  Cheol Soo Choi  ;  Jin Hee Ahn  ;  Byung-Wan Lee  ;  Eun Seok Kang  ;  Bong Soo Cha  ;  Hyun Chul Lee 
Citation
 Metabolism: Clinical and Experimental, Vol.63(6) : 793-799, 2014 
Journal Title
 Metabolism: Clinical and Experimental 
ISSN
 0026-0495 
Issue Date
2014
Abstract
OBJECTIVE: We investigated whether KR-66195, a new synthetic dipeptidyl dipeptidase IV inhibitor, could prevent weight gain, as well as improving glycemic control in diet-induced obese (DIO) and ob/ob mice. MATERIALS/METHODS: Male C57BL/6 mice were randomly assigned to the following groups: chow diet, high-fat diet, and high-fat diet with KR-66195. After KR-66195 treatment for eight weeks, intraperitoneal glucose tolerance tests were performed. A pair-feeding study was performed to investigate the mechanisms of the anti-obesity effects of KR-66195 in DIO mice. Female ob/ob mice were treated with KR-66195 for three weeks and compared to the vehicle-treated group. RESULTS: In DIO mice, KR-66195 treatment increased the plasma glucagon-like peptide (GLP)-1 levels and improved glucose tolerance. This treatment also reduced body weight gain (5.38±0.94 g vs. 12.08±0.55 g, P<0.01) and food intake (2.41±0.09 g vs. 2.79±0.11 g, P<0.05). In ob/ob mice, KR-66195 treatment for three weeks resulted in comparable effects in DIO mice. In the pair-feeding study, KR-66195-treated mice exhibited a 16% increase in energy expenditure (kcal/h/kg lean body mass) without significant differences in body weight or activities compared with pair-fed mice. These results suggest that KR-66195 prevented weight gain in DIO mice by decreasing food intake, as well as increasing energy expenditure. CONCLUSIONS: KR-66195 markedly increased plasma levels of GLP-1, resulting in the probable improvement in glucose tolerance and reduced body weight and food intake. Thus, KR-66195 might be further developed as a therapeutic drug to treat obesity, as well as diabetes.
Full Text
http://www.sciencedirect.com/science/article/pii/S002604951400050X
DOI
10.1016/j.metabol.2014.02.011
Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Kim, Yeon Wook(김연욱)
Lee, Byung Wan(이병완) ORCID logo https://orcid.org/0000-0002-9899-4992
Lee, Eun Young(이은영)
Lee, Hyun Chul(이현철)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99561
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