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Acute In Vivo Administration of Compound 21 Stimulates Akt and ERK1/2 Phosphorylation in Mouse Heart and Adipose

Diego T Quiroga1, Jorge A Narvaéz Pardo1, María G Zubiría2

  • 1Facultad de Farmacia y Bioquímica, Departamento de Química Biológica and IQUIFIB (UBA-CONICET), Universidad de Buenos Aires, Buenos Aires C1113AAD, Argentina.

International Journal of Molecular Sciences
|December 9, 2023
PubMed

Insights

The angiotensin II type 2 (AT2) receptor agonist C21 activates key insulin signaling molecules Akt and ERK1/2 in mice. This activation occurs independently of the insulin receptor (IR), suggesting novel pathways for improved insulin sensitivity.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • The angiotensin II type 2 (AT2) receptor is implicated in enhancing insulin sensitivity.
  • The precise molecular mechanisms of AT2 receptor-mediated insulin facilitation remain unclear.

Purpose of the Study:

  • To determine if acute in vivo administration of the AT2 receptor agonist C21 activates insulin signaling pathways in target tissues.
  • To elucidate the role of the insulin receptor (IR) in AT2 receptor-induced signaling.

Main Methods:

  • Acute intravenous injection of C21 (0.25 mg/kg) in male C57BL/6 mice.
  • Analysis of Akt and ERK1/2 phosphorylation in epididymal white adipose tissue (WAT) and heart tissue.
  • Assessment of insulin receptor (IR) phosphorylation levels.

Main Results:

  • C21 induced significant phosphorylation of Akt and ERK1/2 in both WAT and heart.
  • C21-mediated phosphorylation of Akt and ERK1/2 in WAT was substantial, reaching ~65% of insulin-induced levels.
  • C21 stimulated p-Akt in the heart to a lesser extent than in WAT, and p-ERK1/2 to levels comparable to insulin.
  • Crucially, C21 did not alter insulin receptor (IR) phosphorylation in either tissue.

Conclusions:

  • Acute in vivo administration of the AT2 receptor agonist C21 activates Akt and ERK1/2 signaling.
  • This activation proceeds through a mechanism independent of the insulin receptor (IR).
  • These findings highlight the involvement of Akt and ERK1/2 in AT2 receptor-mediated signaling pathways relevant to insulin sensitivity.
Keywords:
AT2 receptorAktC21ERK1/2signaling

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