Institutional Repository of Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences
| 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
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| 2020-10-01 | |
| 发表期刊 | BRITISH JOURNAL OF PHARMACOLOGY
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| ISSN | 0007-1188 |
| 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 |
| DOI | 10.1111/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 | |
| 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. |
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| Antidiabetic activit（42653KB） | 期刊论文 | 作者接受稿 | 限制开放 | CC BY-NC-SA | 浏览 | |
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