Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Insulin Resistance Disrupts the Interaction Between AKT and the NMDA Receptor and the Inactivation of the CaMKIV/CREB Pathway in Minimal Hepatic Encephalopathy.

Authors: Ding, Saidan  Zhuge, Weishan  Yang, Jianjing  Wen, Fangfang  Xu, Zhu  Wang, Xuebao  Zhuge, Qichuan 
Citation: Ding S, etal., Toxicol Sci. 2017 Oct 1;159(2):290-306. doi: 10.1093/toxsci/kfx093.
Pubmed: (View Article at PubMed) PMID:28505381
DOI: Full-text: DOI:10.1093/toxsci/kfx093

Hepatic cirrhosis-induced Minimal hepatic encephalopathy (MHE) has been characterized for cognitive dysfunction and central nervous system (CNS) insulin resistance (IR) has been acknowledged to be closely correlated with cognitive impairment while hepatic cirrhosis has been recognized to induce IR. Thus, this study aimed to investigate whether CNS IR occurred in MHE and induced MHE, as well as the underlying mechanism. We found IR in the MHE rats, an especially decreased level of the insulin receptor (InsR), and an increased serine phosphorylation of IRS1 in CNS. PI3K/AKT pathway signaling to the phosphorylation of N-Methyl-d-Aspartate receptors (NMDA receptors, NRs, NR1/NR2B) and downstream activation of the CaMKIV/CREB pathway and final production of neurotrophic factors were triggered by insulin, but impaired in the MHE rats. Additionally, CNS IR, memory impairment, the desensitization of the PI3K/AKT/NMDA receptor (NR)/CaMKIV/CREB pathway and decreased production of BDNF/NT3 in MHE rats were improved by rosiglitazone (RSG). These results suggested that IR, which induces the deficits in the insulin-mediated PI3K/AKT/NR/CaMKIV/CREB/neurotrophin pathway and subsequent memory decline, contributes to the pathogenesis of MHE.

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 14700777
Created: 2019-08-16
Species: All species
Last Modified: 2019-08-16
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.