Angiotensin-(1-7) stimulates the phosphorylation of Akt in rat extracardiac tissues in vivo via receptor Mas

Regul Pept. 2010 Apr 9;161(1-3):1-7. doi: 10.1016/j.regpep.2010.02.001. Epub 2010 Feb 25.

Abstract

The in vivo effect of angiotensin (ANG)-(1-7) on the activation of insulin signaling transduction in rat extracardiac tissues is unknown. Thus, in the present study, we evaluated the ability of ANG-(1-7) to stimulate the phosphorylation of Akt, a main mediator of insulin action in rat extracardiac tissues (adipose tissue, liver and skeletal muscle). We proved that ANG-(1-7) induces the phosphorylation of Akt at both threonine 308 and serine 473 in all tissues analyzed. Selective antagonism of the Mas receptor with A779 blocked the ANG-(1-7)-induced Akt phosphorylation in extracardiac tissues. Reinforcing this evidence, we determined that ANG-(1-7) induces the in vivo activation of the downstream target of Akt, glycogen synthase kinase-3beta in liver and skeletal muscle. Moreover, in every tissue analyzed, the presence of the Mas receptor was detected by immunohistochemical analysis. Based on the current results, we postulate that ANG-(1-7) could be a positive physiological contributor to the actions of insulin in extracardiac tissues. Therefore, our findings extend the possibilities for new approaches in the study of ANG-(1-7)/Mas receptor axis and show the therapeutic potential of ANG-(1-7) in the treatment of metabolic disorders such as insulin resistance as well as other disorders associated with diminished Akt activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Angiotensin I / pharmacology*
  • Angiotensin II / analogs & derivatives
  • Angiotensin II / pharmacology
  • Animals
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Immunoblotting
  • Immunohistochemistry
  • In Vitro Techniques
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Peptide Fragments / pharmacology*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / drug effects

Substances

  • 7-Ala-angiotensin (1-7)
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • proto-oncogene proteins c-mas-1
  • Angiotensin II
  • Angiotensin I
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
  • angiotensin I (1-7)