| DA-1229, a novel and potent DPP4 inhibitor, improves insulin resistance and delays the onset of diabetes. | |
| | |
MedLine Citation:
|
PMID: 22056373 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
AIM: To characterize the pharmacodynamic profile of DA-1229, a novel dipeptidyl peptidase (DPP) 4 inhibitor. MAIN METHODS: Enzyme inhibition assays against DPP4, DPP8 and DPP9. Antidiabetic effects of DA-1229 in HF-DIO mice and young db/db mice. KEY FINDINGS: DA-1229 was shown to potently inhibit the DPP4 enzyme in human and murine soluble forms and the human membrane-bound form with IC(50) values of 0.98, 3.59 and 1.26nM, respectively. As a reversible and competitive inhibitor, DA-1229 was more selective to human DPP4 (6000-fold) than to human DPP8 and DPP9. DA-1229 (0.1-3mg/kg) dose-dependently inhibited plasma DPP4 activity, leading to increased levels of plasma GLP-1 and insulin, and thereby lowering blood glucose levels in mice. In high fat diet-fed (HF) mice, a single oral dose of 100mg/kg of DA-1229 reduced plasma DPP4 activity by over 80% during a 24h period. Long-term treatment with DA-1229 for 8weeks revealed significant improvements in glucose intolerance and insulin resistance, accompanied by significant body weight reduction. However, it remains unclear whether there is a direct causal relationship between DPP4 inhibition and body weight reduction. In young db/db mice, the DA-1229 treatment significantly reduced blood glucose excursions for the first 2weeks, resulting in significantly lower levels of HbA1c at the end of the study. Furthermore, the pancreatic insulin content of the treatment group was significantly higher than that of the db/db control. SIGNIFICANCE: DA-1229 as a novel and selective DPP4 inhibitor improves the insulin sensitivity in HF mice and delays the onset of diabetes in young db/db mice. |
| | |
Authors:
|
Mi-Kyung Kim; Yu Na Chae; Ha Dong Kim; Eun Kyoung Yang; Eun Jung Cho; Song-Hyen Choi; Ye-Hwang Cheong; Hae-Sun Kim; Heung Jae Kim; Yeong Woo Jo; Moon-Ho Son; Soon-Hoe Kim; Chang Yell Shin |
Related Documents
:
|
21130513 - Effects of multiple doses of the dpp-iv inhibitor pf-734200 on the relationship between... 9119543 - Non-insulin dependent diabetes mellitus: a phenomenon of ageing? 17706903 - Design and in vivo evaluation of a patch delivery system for insulin based on thiolated... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-10-20 |
Journal Detail:
|
Title: Life sciences Volume: - ISSN: 1879-0631 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
|
Created Date: 2011-11-7 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0375521 Medline TA: Life Sci Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011. Published by Elsevier Inc. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Insulin attenuates the acquisition and expression of ethanol-induced locomotor sensitization in DBA/...
Next Document: Lack of modulatory effect of simvastatin on indoxyl sulfate-induced activation of cultured endotheli...