Hepatic β-arrestin 2 is essential for maintaining euglycemia.

Published

Journal Article

An increase in hepatic glucose production (HGP) represents a key feature of type 2 diabetes. This deficiency in metabolic control of glucose production critically depends on enhanced signaling through hepatic glucagon receptors (GCGRs). Here, we have demonstrated that selective inactivation of the GPCR-associated protein β-arrestin 2 in hepatocytes of adult mice results in greatly increased hepatic GCGR signaling, leading to striking deficits in glucose homeostasis. However, hepatocyte-specific β-arrestin 2 deficiency did not affect hepatic insulin sensitivity or β-adrenergic signaling. Adult mice lacking β-arrestin 1 selectively in hepatocytes did not show any changes in glucose homeostasis. Importantly, hepatocyte-specific overexpression of β-arrestin 2 greatly reduced hepatic GCGR signaling and protected mice against the metabolic deficits caused by the consumption of a high-fat diet. Our data support the concept that strategies aimed at enhancing hepatic β-arrestin 2 activity could prove useful for suppressing HGP for therapeutic purposes.

Full Text

Duke Authors

Cited Authors

  • Zhu, L; Rossi, M; Cui, Y; Lee, RJ; Sakamoto, W; Perry, NA; Urs, NM; Caron, MG; Gurevich, VV; Godlewski, G; Kunos, G; Chen, M; Chen, W; Wess, J

Published Date

  • August 2017

Published In

Volume / Issue

  • 127 / 8

Start / End Page

  • 2941 - 2945

PubMed ID

  • 28650340

Pubmed Central ID

  • 28650340

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI92913

Language

  • eng