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Acute and chronic administration of SHR117887, a novel and specific dipeptidyl peptidase-4 inhibitor, improves metabolic control in diabetic rodent models

文献类型：期刊论文

作者Liu, Xiao1; Zhang, Li-na1; Feng, Ying1; Zhang, Lei2; Qu, Hui1; Cao, Guo-qing2; Leng, Ying1
刊名ACTA PHARMACOLOGICA SINICA
出版日期2012-08
卷号33期号:8页码:1013-1022
关键词SHR117887 vildagliptin (LAF237) dipeptidyl peptidase-4 (DPP-4) type 2 diabetes mellitus glucagon-like peptide-1 (GLP-1) insulin beta-cells
ISSN号1671-4083
DOI10.1038/aps.2012.75
文献子类Article
英文摘要Aim: Dipeptidyl deptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents. The purpose of this study was to assess the acute and chronic effects of SHR117887, a novel DPP-4 inhibitor, on metabolic control and pancreatic beta-cell function in normal or diabetic rodent models. Methods: In the acute experiments, ICR mice, diet-induced obese (DIO) rats and ob/ob mice were subjected to an oral glucose tolerance test (OGTT) following a single oral administration of SHR117887 (0.1, 0.3, 1, or 3 mg/kg). Blood samples were collected to measure glucose, insulin, DPP-4 activity and active GLP-1 level. In the chronic experiments, ob/ob mice was administered SHR117887 (3, 10, or 30 mg/kg) twice daily for 33 d to assess the effects on metabolic control and pancreatic beta-cell function. Vildagliptin (LAF237) was used as a positive control in all the experiments. Results: Acute oral administration of SHR117887 dose-dependently decreased the serum DPP-4 activity and improved glucose tolerance in ICR mice, DIO rats and ob/ob mice. This was accompanied by significant increases in the serum active GLP-1 and insulin levels. Chronic administration of SHR117887 significantly decreased fasting blood glucose level and improved the lipid profiles in ob/ob mice by reducing the serum triglyceride and free fatty acid levels, and its efficacy was comparable with that of vildagliptin at the same molarity. Moreover, chronic administration of SHR117887 increased the insulin staining of islet cells, which is suggestive of improved beta-cell function. Conclusion: SHR117887 is a potent DPP-4 inhibitor that improves metabolic control and beta-cell function in diabetic rodent models, suggesting that it could be a new therapeutic agent for the treatment of type 2 diabetes.
WOS关键词GLUCAGON-LIKE PEPTIDE-1 ; IMPROVED GLUCOSE-TOLERANCE ; DRUG-NAIVE PATIENTS ; BETA-CELL FUNCTION ; GLYCEMIC CONTROL ; IV INHIBITOR ; INSULIN-SECRETION ; DOUBLE-BLIND ; ZUCKER RATS ; EFFICACY
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000307233900006
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/278000]  
专题药理学第一研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药物化学研究室
通讯作者Leng, Ying
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
2.Shanghai Hengrui Pharmaceut Co Ltd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Xiao,Zhang, Li-na,Feng, Ying,et al. Acute and chronic administration of SHR117887, a novel and specific dipeptidyl peptidase-4 inhibitor, improves metabolic control in diabetic rodent models[J]. ACTA PHARMACOLOGICA SINICA,2012,33(8):1013-1022.
APA Liu, Xiao.,Zhang, Li-na.,Feng, Ying.,Zhang, Lei.,Qu, Hui.,...&Leng, Ying.(2012).Acute and chronic administration of SHR117887, a novel and specific dipeptidyl peptidase-4 inhibitor, improves metabolic control in diabetic rodent models.ACTA PHARMACOLOGICA SINICA,33(8),1013-1022.
MLA Liu, Xiao,et al."Acute and chronic administration of SHR117887, a novel and specific dipeptidyl peptidase-4 inhibitor, improves metabolic control in diabetic rodent models".ACTA PHARMACOLOGICA SINICA 33.8(2012):1013-1022.

入库方式： OAI收割

来源：上海药物研究所

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