RGD Reference Report - Aldosterone induces vascular insulin resistance by increasing insulin-like growth factor-1 receptor and hybrid receptor. - Rat Genome Database

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Aldosterone induces vascular insulin resistance by increasing insulin-like growth factor-1 receptor and hybrid receptor.

Authors: Sherajee, SJ  Fujita, Y  Rafiq, K  Nakano, D  Mori, H  Masaki, T  Hara, T  Kohno, M  Nishiyama, A  Hitomi, H 
Citation: Sherajee SJ, etal., Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):257-63. doi: 10.1161/ATVBAHA.111.240697. Epub 2011 Dec 15.
RGD ID: 10045990
Pubmed: PMID:22173225   (View Abstract at PubMed)
DOI: DOI:10.1161/ATVBAHA.111.240697   (Journal Full-text)

OBJECTIVE: We previously showed that aldosterone induces insulin resistance in rat vascular smooth muscle cells (VSMCs). Because insulin-like growth factor-1 receptor (IGF1R) affects insulin signaling, we hypothesized that aldosterone induces vascular insulin resistance and remodeling via upregulation of IGF1R and its hybrid insulin/insulin-like growth factor-1 receptor. METHODS AND RESULTS: Hybrid receptor expression was measured by immunoprecipitation. Hypertrophy of VSMCs was evaluated by (3)H-labeled leucine incorporation. Aldosterone (10 nmol/L) significantly increased protein and mRNA expression of IGF1R and hybrid receptor in VSMCs but did not affect insulin receptor expression. Mineralocorticoid receptor blockade with eplerenone inhibited aldosterone-induced increases in IGF1R and hybrid receptor. Aldosterone augmented insulin (100 nmol/L)-induced extracellular signal-regulated kinase 1/2 phosphorylation. Insulin-induced leucine incorporation and alpha-smooth muscle actin expression were also augmented by aldosterone in VSMCs. These aldosterone-induced changes were significantly attenuated by eplerenone or picropodophyllin, an IGF1R inhibitor. Chronic infusion of aldosterone (0.75 mug/hour) increased blood pressure and aggravated glucose metabolism in rats. Expression of hybrid receptor, azan-positive area, and oxidative stress in aorta was increased in aldosterone-infused rats. Spironolactone and tempol prevented these aldosterone-induced changes. CONCLUSIONS: Aldosterone induces vascular remodeling through IGF1R- and hybrid receptor-dependent vascular insulin resistance. Mineralocorticoid receptor blockade may attenuate angiopathy in hypertensive patients with hyperinsulinemia.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to aldosterone  IEP 10045990 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPIInsr (Rattus norvegicus)10045990 RGD 
protein binding  IPIIgf1r (Rattus norvegicus)10045990 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Igf1r  (insulin-like growth factor 1 receptor)
Insr  (insulin receptor)


Additional Information