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

Muscle Metabolism Laboratory, Department of Physiology, University of Arizona College of Medicine, Tucson, AZ 85721-0093, USA.

Biochemical and biophysical research communications 2012 Sep 28

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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 (500 nM for 2 h) decreased insulin-stimulated glucose transport activity by 45% (P < 0.05). In the presence of 500-1000 nM 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 Ser(473) phosphorylation (47%, P < 0.05) without an effect on glycogen synthase kinase-3β Ser(9) 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 Ser(473) phosphorylation in soleus muscle were completely prevented in presence of 1000 nM 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. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

Mujalin Prasannarong, Fernando R Santos, Erik J Henriksen. ANG-(1-7) reduces ANG II-induced insulin resistance by enhancing Akt phosphorylation via a Mas receptor-dependent mechanism in rat skeletal muscle. Biochemical and biophysical research communications. 2012 Sep 28;426(3):369-73