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 | |
| 2020-10-01 | |
| Source Publication | BRITISH JOURNAL OF PHARMACOLOGY
 |
| ISSN | 0007-1188 |
| Volume | 177Issue:19Pages:4464-4480 |
| Abstract | 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. |
| Keyword | bromophenol PTP1B inhibitor selectivity cell permeability oral bioavailability |
| DOI | 10.1111/bph.15195 |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | 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 Research Area | Pharmacology & Pharmacy |
| WOS Subject | Pharmacology & Pharmacy |
| WOS ID | WOS:000563751300001 |
| Publisher | WILEY |
| Citation statistics | |
| Document Type | 期刊论文 |
| Version | 出版稿 |
| Identifier | http://ir.qdio.ac.cn/handle/337002/168280 |
| Collection | 实验海洋生物学重点实验室 |
| Corresponding Author | Luo, Jiao; Shi, Dayong |
| Affiliation | 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 |
| First Author Affilication | Institute of Oceanology, Chinese Academy of Sciences |
| Corresponding Author Affilication | Institute of Oceanology, Chinese Academy of Sciences |
| Recommended Citation 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. |
| Files in This Item: | ||||||
| File Name/Size | DocType | Version | Access | License | ||
| Antidiabetic activit（42653KB） | 期刊论文 | 作者接受稿 | 开放获取 | CC BY-NC-SA | View | |
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment