계명대학교 의학도서관 Repository

Adenovirus-mediated overexpression of Tcfe3 ameliorates hyperglycaemia in a mouse model of diabetes by upregulating glucokinase in the liver

Metadata Downloads
Author(s)
M. Y. KimS. H. JoJ. M. ParkT. H. KimS. S. ImY. H. Ahn
Keimyung Author(s)
Im, Seung Soon
Department
Dept. of Physiology (생리학)
Journal Title
Diabetologia
Issued Date
2013
Volume
56
Issue
3
Abstract
Aims/hypothesis Transcription factor E3 (TFE3) has been
shown to increase insulin sensitivity by activating insulinsignalling
pathways. However, the role of TFE3 in glucose homeostasis
is not fully understood. Here, we explored the possible
therapeutic potential of TFE3 for the control of hyperglycaemia
using a streptozotocin-induced mouse model of diabetes.
Methods We achieved overabundance of TFE3 in streptozotocin
mice by administering an adenovirus (Ad) or adenoassociated
virus serotype 2 (AAV2). We also performed an
oral glucose tolerance test (OGTT) and insulin tolerance test
(ITT). To explore molecular mechanisms of blood glucose
control by TFE3, transcriptional studies on the regulation of
genes involved in hepatic glucose metabolism were performed
using quantitative real-time PCR and chromatin
immunoprecipitation assay. The binding site of TFE3 in
the liver Gck gene promoter was identified using deletion
and site-specific mutation studies.
Results Overabundance of TFE3 resulted in reduced
hyperglycaemia as shown by the OGTT and ITT in
streptozotocin-treated mice. We observed that TFE3 can
upregulate Gck in a state of insulin deficiency. However,
glucose-6-phosphatase and cytosolic phosphoenolpyruvate
carboxykinase mRNA levels were decreased by Admediated
overexpression of Tcfe3. Biochemical studies
revealed that the anti-hyperglycaemic effect of TFE3 is
due to the upregulation of Gck. In primary cultured hepatocytes,
TFE3 increased expression of Gck mRNA. Conversely,
small interfering RNA-mediated knockdown of TFE3
resulted in a decrease in Gck mRNA.
Conclusions/interpretation This study demonstrates that
TFE3 counteracts hyperglycaemia in streptozotocin-treated
mice. This effect could be due to the upregulation of Gck by
binding of TFE3 to its cognitive promoter region.
Keywords Liver-type glucokinase (Gck) . TFE3 .
Transcription factor E3 . Type 1 diabetes mellitus .
Transcriptional regulation . Streptozotocin
Keimyung Author(s)(Kor)
임승순
Publisher
School of Medicine
Citation
M. Y. Kim et al. (2013). Adenovirus-mediated overexpression of Tcfe3 ameliorates
hyperglycaemia in a mouse model of diabetes by upregulating
glucokinase in the liver. Diabetologia, 56(3), 635–643. doi: 10.1007/s00125-012-2807-7
Type
Article
ISSN
0012-186X
Source
http://link.springer.com/content/pdf/10.1007%2Fs00125-012-2807-7.pdf
DOI
10.1007/s00125-012-2807-7
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35584
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
공개 및 라이선스
  • 공개 구분공개
  • 엠바고Forever
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.