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| Status |
Public on Feb 06, 2017 |
| Title |
Hypothalamic oxidative stress provokes leptin and insulin resistance [Islets] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| 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.
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| Overall design |
Gene expression in the pancreatic islets 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.
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| Contributor(s) |
Yagishita Y, Uruno A, Fukutomi T, Saito R, Saigusa D, Pi J, Fukamizu A, Sugiyama F, Takahashi S, Yamamoto M |
| Citation missing |
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| |
| Submission date |
Dec 11, 2016 |
| Last update date |
Nov 01, 2017 |
| Contact name |
Akira Uruno |
| E-mail(s) |
[email protected]
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| Phone |
81-22-717-8085
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| Organization name |
Tohoku University Graduate School of Medicine
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| Street address |
2-1 Seiryo-cho, Aoba-ku
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| City |
Sendai |
| State/province |
Miyagi |
| ZIP/Postal code |
980-8575 |
| Country |
Japan |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE92236 |
Hypothalamic oxidative stress provokes leptin and insulin resistance |
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| Relations |
| BioProject |
PRJNA356977 |
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