PMID- 31756973
OWN - NLM
STAT- MEDLINE
DCOM- 20200414
LR  - 20200414
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 24
IP  - 23
DP  - 2019 Nov 20
TI  - Deficiency of Urokinase Plasminogen Activator May Impair beta Cells Regeneration and 
      Insulin Secretion in Type 2 Diabetes Mellitus.
LID - 10.3390/molecules24234208 [doi]
LID - 4208
AB  - : Background: The relationship between urokinase-type plasminogen activator (uPA) 
      and the development of type 2 diabetes mellitus (T2DM) was investigated in the 
      study by using mice and cell models, as well as patients with T2DM. METHODS: In 
      mice models, wild-type and uPA knockout (uPA-/-) BALB/c mice were used for 
      induction of T2DM. In cell models, insulin secretion rate and beta cell 
      proliferation were assessed in normal and high glucose after treating uPA siRNA, 
      uPA, or anti-uPA antibody. In our clinical study, patients with T2DM received an 
      oral glucose-tolerance test, and the relationship between uPA and insulin 
      secretion was assessed. RESULTS: Insulin particles and insulin secretion were 
      mildly restored one month after induction in wild-type mice, but not in uPA-/- 
      mice. In cell models, insulin secretion rate and cell proliferation declined in 
      high glucose after uPA silencing either by siRNA or by anti-uPA antibody. After 
      treatment with uPA, beta cell proliferation increased in normal glucose. In clinical 
      study, patients with T2DM and higher uPA levels had better ability of insulin 
      secretion than those with lower uPA levels. CONCLUSION: uPA may play a 
      substantial role in insulin secretion, beta cell regeneration, and progressive 
      development of T2DM. Supplementation of uPA might be a novel approach for 
      prevention and treatment of T2DM in the future.
FAU - Wu, Chung-Ze
AU  - Wu CZ
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, School 
      of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, 
      Taiwan.
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang 
      Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
FAU - Ou, Shih-Hsiang
AU  - Ou SH
AD  - Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans 
      General Hospital, Kaohsiung 81362, Taiwan.
FAU - Chang, Li-Chien
AU  - Chang LC
AD  - School of Pharmacy, National Defense Medical Center, Taipei 11490, Taiwan.
FAU - Lin, Yuh-Feng
AU  - Lin YF
AD  - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical 
      University, Taipei 11031, Taiwan.
AD  - Deputy Superintendent, Shuang Ho Hospital, Taipei Medical University, New Taipei 
      City 23561, Taiwan.
FAU - Pei, Dee
AU  - Pei D
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Fu Jen 
      Catholic University Hospital, New Taipei City 24352, Taiwan.
AD  - School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 
      City 24205, Taiwan.
FAU - Chen, Jin-Shuen
AU  - Chen JS
AD  - Department of Education and Research, Kaohsiung Veterans General Hospital, 
      Kaohsiung 81362, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20191120
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Experimental/genetics/*metabolism/pathology
MH  - Diabetes Mellitus, Type 2/genetics/*metabolism/pathology
MH  - Insulin-Secreting Cells/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - *Regeneration
MH  - Urokinase-Type Plasminogen Activator/*deficiency/metabolism
PMC - PMC6930534
OTO - NOTNLM
OT  - insulin secretion
OT  - type 2 diabetes mellitus
OT  - urokinase plasminogen activator
OT  - beta cell regeneration
COIS- The authors declare no conflicts of interest
EDAT- 2019/11/24 06:00
MHDA- 2020/04/15 06:00
PMCR- 2019/11/20
CRDT- 2019/11/24 06:00
PHST- 2019/08/29 00:00 [received]
PHST- 2019/11/05 00:00 [revised]
PHST- 2019/11/16 00:00 [accepted]
PHST- 2019/11/24 06:00 [entrez]
PHST- 2019/11/24 06:00 [pubmed]
PHST- 2020/04/15 06:00 [medline]
PHST- 2019/11/20 00:00 [pmc-release]
AID - molecules24234208 [pii]
AID - molecules-24-04208 [pii]
AID - 10.3390/molecules24234208 [doi]
PST - epublish
SO  - Molecules. 2019 Nov 20;24(23):4208. doi: 10.3390/molecules24234208.