RGD Reference Report - Upregulation of miR-497 induces hepatic insulin resistance in E3 rats with HFD-MetS by targeting insulin receptor. - Rat Genome Database

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Upregulation of miR-497 induces hepatic insulin resistance in E3 rats with HFD-MetS by targeting insulin receptor.

Authors: Wang, X  Wang, M  Li, H  Lan, X  Liu, L  Li, J  Li, Y  Li, J  Yi, J  Du, X  Yan, J  Han, Y  Zhang, F  Liu, M  Lu, S  Li, D 
Citation: Wang X, etal., Mol Cell Endocrinol. 2015 Nov 15;416:57-69. doi: 10.1016/j.mce.2015.08.021. Epub 2015 Aug 20.
RGD ID: 11529553
Pubmed: PMID:26300412   (View Abstract at PubMed)
DOI: DOI:10.1016/j.mce.2015.08.021   (Journal Full-text)

OBJECTIVE: The study aims to find regulatory microRNA(s) responsible for down-regulated insulin receptor (InsR) in the liver of HFD-MetS E3 rats with insulin resistance. METHODS: Firstly, hepatic insulin resistance in HFD-MetS E3 rats was evaluated by RT-qPCR, western blotting, immunohistochemistry and PAS staining. Secondly, the candidate miRNAs targeting rat InsR were predicted through online softwares and detected in the liver of HFD-MetS E3 rats with insulin resistance. Then, the expression of InsR, phosphorylated IRS-1 (pIRS-1) at Tyr632, phosphorylated AKTs (pAKTs) at Ser473 and Thr308, phosphorylated GSK-3beta (p GSK-3beta) at Ser9, phosphorylated GS (pGS) at Ser641 and the glycogen content were detected in CBRH-7919 cells treated with 100 nM insulin for different time periods by western blotting or PAS staining respectively, after transient transfection with miR-497 mimics or inhibitors for 24 h. Lastly, the relation between miR-497 and InsR was further determined using dual luciferase reporter assay. RESULTS: Elevated miR-497 was negatively related with down-regulated InsR in the liver of HFD-MetS E3 rats with insulin resistance. Comparing with the mNC group, glycogen content and the expression of InsR, pIRS-1 (Tyr632), pAKTs (Ser473 and Thr308) and pGSK-3beta (Ser9) decreased significantly in CBRH-7919 cells, while pGS (Ser641) increased significantly, after transient transfection with miR-497 mimics for 24 h and treatment with 100 nM insulin for corresponding time periods, counter to those results in CBRH-7919 cells after similar procedures with miR-497 inhibitors and insulin. In addition, dual luciferase reporter assay further confirmed that miR-497 can bind to the 3'UTR of rat InsR. CONCLUSION: Insulin receptor is the target gene of miR-497, and elevated miR-497 might induce hepatic insulin resistance in HFD-MetS E3 Rats through inhibiting the expression of insulin receptor and confining the activation of IRS-1/PI3K/Akt/GSK-3beta/GS pathway to insulin.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
INSRHumanInsulin Resistance disease_progressionISOInsr (Rattus norvegicus)mRNA and protein:decreased expression:liver (rat)RGD 
InsrRatInsulin Resistance disease_progressionIEP mRNA and protein:decreased expression:liver (rat)RGD 
InsrMouseInsulin Resistance disease_progressionISOInsr (Rattus norvegicus)mRNA and protein:decreased expression:liver (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
InsrRatinsulin receptor signaling pathway  IEP  RGD 
InsrRatnegative regulation of glycogen biosynthetic process  IEP  RGD 
InsrRatresponse to nutrient levels  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Insr  (insulin receptor)

Genes (Mus musculus)
Insr  (insulin receptor)

Genes (Homo sapiens)
INSR  (insulin receptor)


Additional Information