The effect of insulin treatment versus insulin resistance on microRNA expression in the hypothalamic neuronal cell line mHypoE-46.
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ABSTRACT:
PROVIDER: PRJNA518090 | ENA |
REPOSITORIES: ENA
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Project description: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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