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Series GSE92235 Query DataSets for GSE92235
Status Public on Feb 06, 2017
Title Hypothalamic oxidative stress provokes leptin and insulin resistance [hypothlamus]
Organism Mus musculus
Experiment type Expression profiling by array
Summary The relationship between loss of hypothalamic function and onset of diabetes mellitus remains elusive. Therefore, we generated a targeted oxidative-stress murine model utilizing conditional knockout of selenocysteine-tRNA (Trsp) using rat insulin promoter-driven-Cre (RIP-Cre). These Trsp-knockout (TrspRIPKO) mice exhibit deletion of Trsp in both hypothalamic cells and pancreatic β-cells leading to increased hypothalamic oxidative stress and severe insulin resistance. Leptin signals were suppressed and numbers of proopiomelanocortin-positive neurons in the hypothalamus were decreased. In contrast, a Trsp-knockout mouse (TrspIns1KO) expressing Cre specifically in pancreatic β-cells, but not in the hypothalamus, did not display insulin and leptin resistance, demonstrating a critical role of the hypothalamus in the onset of diabetes mellitus. Nrf2 (NF-E2-related-factor-2) regulates antioxidant gene expression. Gene-driven increase in Nrf2 signaling suppressed hypothalamic oxidative stress and improved insulin and leptin resistance in TrspRIPKO mice. Thus, Nrf2 harbors the potential to prevent the onset of diabetic mellitus by reducing hypothalamic oxidative damage.
 
Overall design Gene expression in the hypothalamus of TrspFlox/Flox (TrspFF), TrspFlox/Flox::RIP-Cre (Trsp-RIPKO) and TrspFlox/Flox::Ins1-Cre (Trsp-Ins1KO) mice. The conditional knockout of Trsp exhibits elevation of oxidative stress.
 
Contributor(s) Yagishita Y, Uruno A, Fukutomi T, Saito R, Saigusa D, Pi J, Fukamizu A, Sugiyama F, Takahashi S, Yamamoto M
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Submission date Dec 11, 2016
Last update date Nov 01, 2017
Contact name Akira Uruno
E-mail aurno02821@gmail.com
Phone 81-22-717-8085
Organization name Tohoku University Graduate School of Medicine
Street address 2-1 Seiryo-cho, Aoba-ku
City Sendai
State/province Miyagi
ZIP/Postal code 980-8575
Country Japan
 
Platforms (1)
GPL11202 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version)
Samples (6)
GSM2424340 TrspFF hypothlamus 1
GSM2424341 TrspFF hypothlamus 2
GSM2424342 Trsp-RIPKO hypothlamus 1
This SubSeries is part of SuperSeries:
GSE92236 Hypothalamic oxidative stress provokes leptin and insulin resistance
Relations
BioProject PRJNA356976

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE92235_RAW.tar 13.0 Mb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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