Insulin induces IRS2-dependent and GRK2-mediated β2AR internalization to attenuate βAR signaling in cardiomyocytes

Qin Fu, Bing Xu, Dippal Parikh, David Cervantes, Yang Kevin Xiang

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The counter-regulatory effects of insulin and catecholamines on carbohydrate and lipid metabolism are well studied, whereas the details of insulin regulation of β adrenergic receptor (βAR) signaling pathway in heart remain unknown. Here, we characterize a novel signaling pathway of insulin receptor (IR) to G protein-coupled receptor kinase 2 (GRK2) in the heart. Insulin stimulates recruitment of GRK2 to β2AR, which induces β2AR phosphorylation at the GRK sites of serine 355/356 and subsequently β2AR internalization. Insulin thereby suppresses βAR-induced cAMP-PKA activities and contractile response in neonatal and adult mouse cardiomyocytes. Deletion of insulin receptor substrate 2 (IRS2) disrupts the complex of IR and GRK2, which attenuates insulin-mediated β2AR phosphorylation at the GRK sites and β2AR internalization, and the counter-regulation effects of insulin on βAR signaling. These data indicate the requirements of IRS2 and GRK2 for insulin to stimulate counter-regulation of βAR via β2AR phosphorylation and internalization in cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)707-715
Number of pages9
JournalCellular Signalling
Volume27
Issue number3
DOIs
StatePublished - Mar 1 2015

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G-Protein-Coupled Receptor Kinase 2
Insulin Receptor Substrate Proteins
Cardiac Myocytes
Adrenergic Receptors
Insulin
Insulin Receptor
Phosphorylation
Carbohydrate Metabolism
Lipid Metabolism
Serine
Catecholamines

Keywords

  • Adrenergic receptor
  • CAMP
  • Cardiac contractility
  • GRK2
  • Insulin receptor
  • Internalization

ASJC Scopus subject areas

  • Cell Biology

Cite this

Insulin induces IRS2-dependent and GRK2-mediated β2AR internalization to attenuate βAR signaling in cardiomyocytes. / Fu, Qin; Xu, Bing; Parikh, Dippal; Cervantes, David; Xiang, Yang Kevin.

In: Cellular Signalling, Vol. 27, No. 3, 01.03.2015, p. 707-715.

Research output: Contribution to journalArticle

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AU - Xiang, Yang Kevin

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