Institutional Repository of Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences
| Highly Selective Protein Tyrosine Phosphatase Inhibitor, 2,2 ',3,3 '-Tetrabromo-4,4 ',5,5 '-tetrahydroxydiphenylmethane, Ameliorates Type 2 Diabetes Mellitus in BKS db Mice | |
| Li, Chao1,2,3,4; Luo, Jiao1,2,3,4; Guo, Shuju1,2,3; Jia, Xiaoling1,2,3; Guo, Chuanlong1,2,3,4; Li, Xiangqian1,2,3; Xu, Qi1,2,3,4; Shi, Dayong1,2,3,4,5 | |
| 2019-05-01 | |
| Source Publication | MOLECULAR PHARMACEUTICS
 |
| ISSN | 1543-8384 |
| Volume | 16Issue:5Pages:1839-1850 |
| Corresponding Author | Shi, Dayong(shidayong@qdio.ac.cn) |
| Abstract | Protein tyrosine phosphatase 1B (PTP1B) is a widely confirmed target of the type 2 diabetes mellitus (T2DM) treatment. Herein, we reported a highly specific PTP1B inhibitor 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxy-diphenylmethane (compound 1), which showed promising hypoglycemic activity in diabetic BKS db mice. With the IC50 value of 2.4 mu M, compound 1 could directly bind to the catalytic pocket of PTP1B through a series of hydrogen bonds. Surface plasmon resonance analysis revealed that the target PTP1B affinity [KD (equilibrium dissociation constant) value] of compound 1 binding to PTP1B was 2.90 mu M. Moreover, compound 1 could activate the insulin signaling pathway in C2C12 skeletal muscle cells. We further evaluated the long-term effects of compound 1 in diabetic BKS db mice. Notably, oral administration of compound 1 significantly reduced the blood glucose levels of diabetic mice with increasing insulin sensitivity. In addition, the dyslipidemia of diabetic mice was also significantly improved by compound 1 gavage. The histological experiments showed that compound 1 treatment significantly ameliorated the disordered hepatic and pancreatic architecture and increased the glycogen content in the liver tissues as well as improved the insulin secretion function of pancreas. Taken together, our results manifested that the natural product compound 1 was a highly specific PTP1B inhibitor, which could activate insulin signaling pathway and ameliorate hyperglycemia and dyslipidemia in diabetic BKS db mice. |
| Keyword | type 2 diabetes mellitus protein tyrosine phosphatase 1B insulin resistance hypoglycemic activity dyslipidemia |
| DOI | 10.1021/acs.molpharmaceut.8b01106 |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | National Natural Science Foundation of China[81773586] ; National Natural Science Foundation of China[81703354] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-DQC014] ; 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] ; Shandong Provincial Natural Science Foundation for Distinguished Young Scholars[JQ201722] ; National Program for Support of Top-notch Young Professionals ; Taishan scholar Youth Project of Shandong province |
| WOS Research Area | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| WOS Subject | Medicine, Research & Experimental ; Pharmacology & Pharmacy |
| WOS ID | WOS:000467351300005 |
| Publisher | AMER CHEMICAL SOC |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.qdio.ac.cn/handle/337002/161338 |
| Collection | 实验海洋生物学重点实验室 |
| Corresponding Author | Shi, Dayong |
| Affiliation | 1.Chinese Acad Sci, Inst Oceanol, CAS Key Lab Expt Marine Biol, Qingdao 266071, Shandong, Peoples R China 2.Qngdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao 266237, Shandong, Peoples R China 3.Chinese Acad Sci, Ctr Ocean Mega Sci, 7 Nanhai Rd, Qingdao 266071, Shandong, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Shandong Univ, State Key Lab Microbial Technol, Qingdao, Shandong, 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 | Li, Chao,Luo, Jiao,Guo, Shuju,et al. Highly Selective Protein Tyrosine Phosphatase Inhibitor, 2,2 ',3,3 '-Tetrabromo-4,4 ',5,5 '-tetrahydroxydiphenylmethane, Ameliorates Type 2 Diabetes Mellitus in BKS db Mice[J]. MOLECULAR PHARMACEUTICS,2019,16(5):1839-1850. |
| APA | Li, Chao.,Luo, Jiao.,Guo, Shuju.,Jia, Xiaoling.,Guo, Chuanlong.,...&Shi, Dayong.(2019).Highly Selective Protein Tyrosine Phosphatase Inhibitor, 2,2 ',3,3 '-Tetrabromo-4,4 ',5,5 '-tetrahydroxydiphenylmethane, Ameliorates Type 2 Diabetes Mellitus in BKS db Mice.MOLECULAR PHARMACEUTICS,16(5),1839-1850. |
| MLA | Li, Chao,et al."Highly Selective Protein Tyrosine Phosphatase Inhibitor, 2,2 ',3,3 '-Tetrabromo-4,4 ',5,5 '-tetrahydroxydiphenylmethane, Ameliorates Type 2 Diabetes Mellitus in BKS db Mice".MOLECULAR PHARMACEUTICS 16.5(2019):1839-1850. |
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