Boc5, a Non-Peptidic Glucagon-Like Peptide-1 Receptor Agonist, Invokes Sustained Glycemic Control and Weight Loss in Diabetic Mice
文献类型：期刊论文
| 作者 | Su, Haoran1; He, Min1; Li, Hongmei1; Liu, Qing1,2; Wang, Jia1 ; Wang, Yiqian1; Gao, Weiwei1; Zhou, Ling1; Liao, Jiayu1; Young, Andrew A.1
|
| 刊名 | PLOS ONE
 |
| 出版日期 | 2008-08-06 |
| 卷号 | 3期号:8 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0002892 |
| 文献子类 | Article |
| 英文摘要 | Background: Our recent discovery of the substituted cyclobutane Boc5, one of the first non-peptidic agonists at glucagon-like peptide-1 receptors, offers the potential of combining oral availability with full agonism capable of eliciting antidiabetic and antiobesity effects. The present study was aimed at determining the in vivo pharmacologic properties of Boc5 in both normal and diabetic mice following chronic administration, with emphasis on glycemic control and weight loss. Methodology/Principal Findings: C57BL/6J and db/db mice were treated daily with Boc5 for 4 weeks and a range of pharmacologic parameters, including hemoglobin A1c, intraperitoneal glucose tolerance, insulin tolerance, fasting insulin and leptin levels, food intake, body weight and fat mass, were assessed before and after the treatment. Effects on food intake, gastric emptying, and insulinogenic index were also investigated in animals acutely administered with Boc5. Boc5 (3 mg) was able to induce a durable restoration of glycemic control (normalization of both hemoglobin A1c and intraperitoneal glucose tolerance) in db/db mice, following 4 weeks of daily administration. As with peptidic glucagon-like peptide-1 receptor agonists, its glycemic benefit and weight (fat) loss were associated with dose-dependent effects that included reduction in food intake, slowing of gastric emptying (both of which reduce nutrient-drive at beta-cells), stimulation of insulin secretion (which was glucose-dependent), and elevation in insulin sensitivity. There was little effect on normal mice treated in the same manner. Conclusions/Significance: Our findings suggest that Boc5 is the only non-peptidic molecule reported thus far to simultaneously activate this spectrum of antidiabetic effects. |
| 资助项目 | Ministry of Science and Technology[2004CB518902] ; Chinese Academy of Sciences[KSCX1-YW-02-2] ; Chinese Academy of Sciences[KSCX2-YW-R-17] ; Natural Science Foundation of China[30628024] ; Shanghai Science and Technology Development Fund[074319114] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000264366600048 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272843]  |
| 专题 | 国家新药筛选中心 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 |
| 通讯作者 | Su, Haoran |
| 作者单位 | 1.Natl Ctr Drug Screening, Shanghai, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Su, Haoran,He, Min,Li, Hongmei,et al. Boc5, a Non-Peptidic Glucagon-Like Peptide-1 Receptor Agonist, Invokes Sustained Glycemic Control and Weight Loss in Diabetic Mice[J]. PLOS ONE,2008,3(8). |
| APA | Su, Haoran.,He, Min.,Li, Hongmei.,Liu, Qing.,Wang, Jia.,...&Wang, Ming-Wei.(2008).Boc5, a Non-Peptidic Glucagon-Like Peptide-1 Receptor Agonist, Invokes Sustained Glycemic Control and Weight Loss in Diabetic Mice.PLOS ONE,3(8). |
| MLA | Su, Haoran,et al."Boc5, a Non-Peptidic Glucagon-Like Peptide-1 Receptor Agonist, Invokes Sustained Glycemic Control and Weight Loss in Diabetic Mice".PLOS ONE 3.8(2008). |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。