ANG-(1-7) reduces ANG II-induced insulin resistance by enhancing Akt phosphorylation via a Mas receptor-dependent mechanism in rat skeletal muscle

Mujalin Prasannarong, Fernando R. Santos, Erik J. Henriksen

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

The nonapeptide angiotensin II (ANG II) induces vasoconstriction via the ANG II type I receptor, while its splice product ANG-(1-7) elicits an antihypertensive effect via the Mas receptor. Although a critical role of ANG II in the etiology of skeletal muscle insulin resistance is well documented, the role of the ANG-(1-7)/Mas receptor axis in this context is poorly understood. Therefore, we determined whether ANG-(1-7) is effective in ameliorating the negative effects of ANG II on insulin-stimulated insulin signaling and glucose transport activity in isolated soleus muscle from normotensive lean Zucker rats. ANG II alone (500nM for 2h) decreased insulin-stimulated glucose transport activity by 45% (P<0.05). In the presence of 500-1000nM ANG-(1-7), insulin-stimulated glucose transport activity in muscle exposed to ANG II improved by ∼30% (P<0.05). Moreover, ANG-(1-7) treatment increased Akt Ser473 phosphorylation (47%, P<0.05) without an effect on glycogen synthase kinase-3β Ser9 phosphorylation. The dependence of ANG-(1-7) action on the Mas receptor was assessed using A779 peptide, a selective Mas receptor antagonist. The positive effects of ANG-(1-7) on insulin-stimulated glucose transport activity and Akt Ser473 phosphorylation in soleus muscle were completely prevented in presence of 1000nM A779. In conclusion, the present study demonstrates that ANG-(1-7), via a Mas receptor-dependent mechanism, can ameliorate the inhibitory effect of ANG II on glucose transport activity in mammalian skeletal muscle, associated with enhanced Akt phosphorylation. These results provide further evidence supporting the targeting of the renin-angiotensin system for interventions designed to reduce insulin resistance in skeletal muscle tissue.

Original languageEnglish (US)
Pages (from-to)369-373
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume426
Issue number3
DOIs
StatePublished - Sep 28 2012

Keywords

  • A779 peptide
  • Glucose transport
  • Insulin signaling
  • Soleus muscle

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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