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ANG (1–7) reduces ANG II‐induced insulin resistance by increasing Akt phosphorylation via a Mas receptor‐dependent mechanism in rat skeletal muscle
Author(s) -
Henriksen Erik John,
Prasannarong Mujalin,
Santos Fernando Reyes
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.686.14
Subject(s) - medicine , endocrinology , angiotensin ii , protein kinase b , phosphorylation , chemistry , insulin resistance , insulin , skeletal muscle , receptor , insulin receptor , biology , biochemistry
Angiotensin II (ANG II) induces hypertension via the ANG II type 1 receptor, while angiotensin (1–7) (ANG (1–7)), a peptide derived primarily from ANG II, 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 in isolated soleus muscle strips from lean Zucker rats. ANG II (500 nM for 2 hr) alone decreased insulin‐stimulated glucose transport by 45% (p<0.05). In the presence of 500–1000 nM ANG (1–7), insulin‐stimulated glucose transport in muscle exposed to ANG II improved by ~25% (p<0.05). Moreover, this ANG (1–7)‐mediated improvement in glucose transport was associated with increased Akt Ser467 phosphorylation (47%, p<0.05). The positive effects of ANG (1–7) on insulin‐stimulated glucose transport and Akt phosphorylation were completely blunted in presence of 1000 nM A779, a selective Mas receptor antagonist. The present study demonstrates that ANG (1–7), via a Mas receptor‐dependent mechanism, can partially prevent the inhibitory effect of ANG II on glucose transport in isolated mammalian skeletal muscle, associated with enhanced Akt phosphorylation.