Hepatic β-arrestin 2 is essential for maintaining euglycemia.

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
J Clin Invest. 2017 127 (8): 2941-2945

PMID: 28650340 · PMCID: PMC5531395 · DOI:10.1172/JCI92913

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.

MeSH Terms (22)

Animals beta-Arrestin 1 beta-Arrestin 2 Blood Glucose Cercopithecus aethiops COS Cells Diabetes Mellitus, Type 2 Diet, High-Fat Gene Deletion Gene Expression Regulation Glucagon Hepatocytes Homeostasis Insulin Liver Male Mice Mice, Inbred C57BL Mice, Knockout Phenotype Receptors, Glucagon Signal Transduction

Connections (1)

This publication is referenced by other Labnodes entities:

Links