Gene interactions and pathways from curated databases and text-mining
Cardiovasc Res 2012, PMID: 22012952

Insulin decreases myocardial adiponectin receptor 1 expression via PI3K/Akt and FoxO1 pathway.

Cui, Xiao-Bing; Wang, Cheng; Li, Li; Fan, Dong; Zhou, Yun; Wu, Dan; Cui, Qing-Hua; Fu, Feng-Ying; Wu, Li-Ling

OBJECTIVE

Adiponectin is considered an important adipokine protecting against diabetes, atherosclerosis, and cardiovascular disease. Because adiponectin receptors (AdipoRs) are critical components in the adiponectin signalling cascade, we investigated the effect of insulin on the expression of myocardial AdipoRs and explored the possible molecular mechanism.

RESULTS

The hyperinsulinaemia rat model was induced by infusion of insulin (1 U/day) for 28 days: serum and myocardial adiponectin levels were increased, and skeletal muscle and myocardial AdipoR1 expression and AMP-activated protein kinase (AMPK) phosphorylation were decreased. In primary cultured neonatal rat ventricular myocytes (NRVMs), insulin decreased AdipoR1 but not AdipoR2 expression and AMPK phosphorylation; high glucose had no affect on AdipoRs expression. Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was increased in insulin-treated hearts and in NRVMs. P13K inhibitor LY294002 and Akt1/2 kinase inhibitor but not the ERK1/2 kinase (MEK) inhibitors PD98059 and U0126 blocked the insulin-induced reduction in AdipoR1 expression and AMPK phosphorylation. Insulin induced forkhead/winged helix box gene group O-1 (FoxO1) phosphorylation and translocation from the nucleus to the cytosol, and this was blocked by LY294002. FoxO1 small interfering RNA reduced AdipoR1 expression and AMPK phosphorylation. In electrophoretic mobility shift assay and chromatin immunoprecipitation, FoxO1 bound to the putative site from -167 to -157 bp of the AdipoR1 promoter both in vitro and in living cells; insulin suppressed this binding, which was blocked by LY294002.

CONCLUSIONS

Insulin inhibits myocardial AdipoR1 expression via PI3K/Akt and FoxO1 pathways, and FoxO1 mediates AdipoR1 transcription by binding to its promoter directly.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

AdipoR1 ⊣ insulin: " Akt and extracellular signal regulated kinase 1/2 ( ERK1/2 ) phosphorylation was increased in insulin treated hearts and in NRVMs. P13K inhibitor LY294002 and Akt1/2 kinase inhibitor but not the ERK1/2 kinase ( MEK ) inhibitors PD98059 and U0126 blocked the insulin induced reduction in AdipoR1 expression and AMPK phosphorylation "

AMPK ⊣ insulin: " Akt and extracellular signal regulated kinase 1/2 ( ERK1/2 ) phosphorylation was increased in insulin treated hearts and in NRVMs. P13K inhibitor LY294002 and Akt1/2 kinase inhibitor but not the ERK1/2 kinase ( MEK ) inhibitors PD98059 and U0126 blocked the insulin induced reduction in AdipoR1 expression and AMPK phosphorylation "

AdipoR1 ⊣ Insulin: " Insulin inhibits myocardial AdipoR1 expression via PI3K/Akt and FoxO1 pathways, and FoxO1 mediates AdipoR1 transcription by binding to its promoter directly "

Manually curated Databases

No curated data.