Specific inhibition of plasminogen activator inhibitor 1 reduces blood glucose level by lowering TNF-a - Details

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Abstract：

Aims:　The　study　aims　to　investigate　the　effect　of　plasminogen　activator　inhibitor　1　(PAI-1),　a　primary　inhibitor　of　fibrinolytic　process,　on　blood　glucose　in　type　2　diabetes　mellitus　(T2DM)　and　its　mechanism.　Materials　and　methods:　We　developed　a　highly　potent　and　highly　specific　PAI-1　inhibitor,　named　PAItrap3,　based　on　the　inactivated　urokinase.　Meanwhile,　a　single　point　mutation　of　PAItrap3　(i.e.,　PAItrapNC)　was　parallelly　prepared　as　negative　control.　PAItrap3　was　intravenously　injected　into　type　2　diabetic　(T2D)　mice　and　its　effect　on　metabolic　system　was　evaluated　by　measuring　the　levels　of　blood　glucose,　PAI-1,　and　tumor　necrosis　factor　alpha　(TNF-α)　in　T2D　mice.　Key　findings:　PAItrap3　significantly　reduced　the　high　blood　glucose　level　and　PAI-1　level　in　streptozotocin-induced　T2D　mice.　PAItrapNC　did　not　have　any　hypoglycemic　effect　at　all　on　T2D　mice.　Mechanistically,　both　PAI-1　and　TNF-α　levels　were　attenuated　by　the　administration　of　PAItrap3.　In　addition,　we　observed　that　PAItrap3　reduced　the　amount　of　fat　droplets　in　adipocytes.　Significance:　These　findings　provide　clear　evidence　for　PAI-1　to　participate　in　inflammation　and　obesity　mediated　hyperglycemia,　and　open　up　a　new　prospect　for　the　treatment　of　T2DM　by　PAI-1　inhibition.　©　2020

Keyword：

Adipocytes; Fasting blood glucose (FBG); Inflammation; Plasminogen activator inhibitor 1 (PAI-1); Tumor necrosis factor alpha (TNF-α); Type 2 diabetic (T2D)

Community：

[ 1 ] [Tang, S.]State Key Laboratory of Structural Chemistry, Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
[ 2 ] [Tang, S.]University of Chinese Academy of Sciences, Beijing, 100049, China
[ 3 ] [Liu, W.]State Key Laboratory of Structural Chemistry, Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
[ 4 ] [Liu, W.]University of Chinese Academy of Sciences, Beijing, 100049, China
[ 5 ] [Pan, X.]State Key Laboratory of Structural Chemistry, Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
[ 6 ] [Liu, L.]Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, China
[ 7 ] [Yang, Y.]Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, Guangdong 518055, China
[ 8 ] [Wang, D.]State Key Laboratory of Structural Chemistry, Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
[ 9 ] [Wang, D.]University of Chinese Academy of Sciences, Beijing, 100049, China
[ 10 ] [Xu, P.]State Key Laboratory of Structural Chemistry, Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
[ 11 ] [Huang, M.]College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, China
[ 12 ] [Chen, Z.]State Key Laboratory of Structural Chemistry, Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
[ 13 ] [Chen, Z.]University of Chinese Academy of Sciences, Beijing, 100049, China

Reprint 's Address：

[Huang, M.]College of Chemistry, Fuzhou UniversityChina

Email：

HMD_lab@fzu.edu.cn

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Source ：

Life Sciences

ISSN： 0024-3205

Year： 2020

Volume： 246

5 . 0 3 7

JCR@2020

5 . 2 0 0

JCR@2023

ESI HC Threshold：156

JCR Journal Grade：1

CAS Journal Grade：3

Cited Count：

WoS CC Cited Count： 0

SCOPUS Cited Count：

ESI Highly Cited Papers on the List： 0 Unfold All

WanFang Cited Count：

Chinese Cited Count：

30 Days PV： 2

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