RGD Reference Report - 20-HETE attenuates the response of glucose-stimulated insulin secretion through the AKT/GSK-3β/Glut2 pathway. - Rat Genome Database

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20-HETE attenuates the response of glucose-stimulated insulin secretion through the AKT/GSK-3β/Glut2 pathway.

Authors: Zhang, Bijun  Lai, Guangrui  Wu, Jingjing  Sun, Ru  Xu, Runhong  Yang, Xianghong  Qi, Yafei  Zhao, Yanyan 
Citation: Zhang B, etal., Endocrine. 2016 Nov;54(2):371-382. doi: 10.1007/s12020-016-1031-5. Epub 2016 Aug 27.
RGD ID: 151347627
Pubmed: PMID:27568038   (View Abstract at PubMed)
DOI: DOI:10.1007/s12020-016-1031-5   (Journal Full-text)

We previously generated cytochrome P450 4F2 (CYP4F2) transgenic mice that have high levels of 20-hydroxyeicosatetraenoic acid (20-HETE) production; these mice exhibit both hypertension and hyperglycemia without insulin resistance. Currently, it is unclear whether and how 20-HETE affects insulin secretion, thus resulting in hyperglycemia. In this study, we found that 20-HETE attenuated glucose-stimulated insulin secretion (GSIS) in CYP4F2 transgenic mice as well as in rat insulinoma INS-1E cells treated with 0.5 μM 20-HETE. HET0016, a selective inhibitor of 20-HETE synthesis, reversed the reduction in GSIS leading to a decrease in blood glucose in the transgenic mice. Furthermore, the expression of glucose transporter 2 (Glut2), Ser473 phosphorylation of protein kinase B (AKT), and Ser9 phosphorylation of glycogen synthase kinase-3β (GSK-3β) were decreased in CYP4F2 transgenic mice compared with wild-type mice. In vitro experiments in INS-1E cells revealed that 20-HETE activated the AKT/GSK-3β pathway and thereby decreased Glut2 expression by inhibiting activator protein 1 (AP-1). TWS119, a GSK-3β selective inhibitor, blocked the 20-HETE-mediated reduction in Glut2 expression. Therefore, we concluded that 20-HETE inhibition of Glut2 contributes to the reduction in GSIS, at least in part, through the AKT/GSK-3β/AP-1/Glut2 pathway.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc2a2Ratcellular response to fatty acid  IDA 20-HETE 20-Hydroxyeicosatetraenoic acidRGD 
Slc2a2Ratcellular response to organic cyclic compound  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc2a2  (solute carrier family 2 member 2)


Additional Information