IOCAS-IR  > 实验海洋生物学重点实验室
Antidiabetic activity in vitro and in vivo of BDB, a selective inhibitor of protein tyrosine phosphatase 1B, fromRhodomela confervoides
Luo, Jiao2,3; Zheng, Meiling6; Jiang, Bo3,5; Li, Chao3,5; Guo, Shuju3,5; Wang, Lijun3,5; Li, Xiangqian1,4; Yu, Rilei6; Shi, Dayong1,4
2020-10-01
发表期刊BRITISH JOURNAL OF PHARMACOLOGY
ISSN0007-1188
卷号177期号:19页码:4464-4480
摘要Background and Purpose Protein tyrosine phosphatase (PTP) 1B (PTP1B) plays a critical role in the regulation of obesity, Type 2 diabetes mellitus and other metabolic diseases. However, drug candidates exhibiting PTP1B selectivity and oral bioavailability are currently lacking. Here, the enzyme inhibitory characteristics and pharmacological benefits of 3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (BDB) were investigated in vitro and in vivo. Experimental Approach Surface plasmon resonance (SPR) assay was performed to validate the direct binding of BDB to PTP1B, and Lineweaver-Burk analysis of the enzyme kinetics was used to characterise the inhibition by BDB. Both in vitro enzyme-inhibition assays and SPR experiments were also conducted to study the selectivity exhibited by BDB towards four other PTP-family proteins: TC-PTP, SHP-1, SHP-2, and LAR. C2C12 myotubes were used to evaluate cellular permeability to BDB. Effects of BDB on insulin signalling, hypoglycaemia and hypolipidaemia were investigated in diabetic BKS db mice, after oral gavage. The beneficial effects of BDB on pancreatic islets were examined based on insulin and/or glucagon staining. Key Results BDB acted as a competitive inhibitor of PTP1B and demonstrated high selectivity for PTP1B among the tested PTP-family proteins. Moreover, BDB was cell-permeable and enhanced insulin signalling in C2C12 myotubes. Lastly, oral administration of BDB produced effective antidiabetic effects in spontaneously diabetic mice and markedly improved islet architecture, which was coupled with an increase in the ratio of beta-cells to alpha-cells. Conclusion and Implications BDB application offers a potentially practical pharmacological approach for treating Type 2 diabetes mellitus by selectively inhibiting PTP1B.
关键词bromophenol PTP1B inhibitor selectivity cell permeability oral bioavailability
DOI10.1111/bph.15195
收录类别SCI
语种英语
资助项目National Natural Science Foundation of China[81703354] ; Key research and development project of Shandong province[2018GSF118200] ; NSFC-Shandong Joint Fund[U1706213] ; Shandong Provincial Natural Science Foundation for Distinguished Young Scholars[JQ201722] ; National Program for Support of Top-notch Young Professionals ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-DQC014] ; Fund of Taishan Scholar Project ; Qingdao Marine Biomedical Science and Technology Innovation Center Project[2017-CXZX01-1-1] ; Qingdao Marine Biomedical Science and Technology Innovation Center Project[2017-CXZX01-3-9] ; Key Research and Development Project of Shandong province[2018GSF118208]
WOS研究方向Pharmacology & Pharmacy
WOS类目Pharmacology & Pharmacy
WOS记录号WOS:000563751300001
出版者WILEY
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.qdio.ac.cn/handle/337002/168280
专题实验海洋生物学重点实验室
通讯作者Luo, Jiao; Shi, Dayong
作者单位1.Shandong Univ, State Key Lab Microbial Technol, Jinan 250100, Peoples R China
2.Qingdao Univ, Sch Publ Hlth, Qingdao 266071, Peoples R China
3.Chinese Acad Sci, Inst Oceanol, CAS Key Lab Expt Marine Biol, Qingdao, Peoples R China
4.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China
5.Chinese Acad Sci, Ctr Ocean Megasci, Qingdao, Peoples R China
6.Ocean Univ China, Sch Med & Pharm, Key Lab Marine Drugs, Chinese Minist Educ, Qingdao, Peoples R China
第一作者单位中国科学院海洋研究所
通讯作者单位中国科学院海洋研究所
推荐引用方式
GB/T 7714
Luo, Jiao,Zheng, Meiling,Jiang, Bo,et al. Antidiabetic activity in vitro and in vivo of BDB, a selective inhibitor of protein tyrosine phosphatase 1B, fromRhodomela confervoides[J]. BRITISH JOURNAL OF PHARMACOLOGY,2020,177(19):4464-4480.
APA Luo, Jiao.,Zheng, Meiling.,Jiang, Bo.,Li, Chao.,Guo, Shuju.,...&Shi, Dayong.(2020).Antidiabetic activity in vitro and in vivo of BDB, a selective inhibitor of protein tyrosine phosphatase 1B, fromRhodomela confervoides.BRITISH JOURNAL OF PHARMACOLOGY,177(19),4464-4480.
MLA Luo, Jiao,et al."Antidiabetic activity in vitro and in vivo of BDB, a selective inhibitor of protein tyrosine phosphatase 1B, fromRhodomela confervoides".BRITISH JOURNAL OF PHARMACOLOGY 177.19(2020):4464-4480.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
Antidiabetic activit(42653KB)期刊论文作者接受稿限制开放CC BY-NC-SA浏览
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Luo, Jiao]的文章
[Zheng, Meiling]的文章
[Jiang, Bo]的文章
百度学术
百度学术中相似的文章
[Luo, Jiao]的文章
[Zheng, Meiling]的文章
[Jiang, Bo]的文章
必应学术
必应学术中相似的文章
[Luo, Jiao]的文章
[Zheng, Meiling]的文章
[Jiang, Bo]的文章
相关权益政策
暂无数据
收藏/分享
文件名: Antidiabetic activity in vitro and in vivo of BDB, a selective inhibitor of protein tyrosine phosphatase 1B, from Rhodomela confervoides.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 

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。