Other
14 Authors
- Godlewski G,
- Sakamoto W,
- Chen M,
- Lee RJ,
- Cui Y,
- Rossi M,
- Chen W,
- Gurevich VV,
- Caron MG,
- Zhu L,
- Perry NA,
- Wess J,
- Urs NM,
- Kunos G
| First Author | Zhu L | Year | 2017 |
| Journal | J Clin Invest | Volume | 127 |
| Issue | 8 | Pages | 2941-2945 |
| PubMed ID | 28650340 | Mgi Jnum | J:246970 |
| Mgi Id | MGI:5916502 | Doi | 10.1172/JCI92913 |
| Citation | Zhu L, et al. (2017) Hepatic beta-arrestin 2 is essential for maintaining euglycemia. J Clin Invest 127(8):2941-2945 |
| abstractText | 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 beta-arrestin 2 in hepatocytes of adult mice results in greatly increased hepatic GCGR signaling, leading to striking deficits in glucose homeostasis. However, hepatocyte-specific beta-arrestin 2 deficiency did not affect hepatic insulin sensitivity or beta-adrenergic signaling. Adult mice lacking beta-arrestin 1 selectively in hepatocytes did not show any changes in glucose homeostasis. Importantly, hepatocyte-specific overexpression of beta-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 beta-arrestin 2 activity could prove useful for suppressing HGP for therapeutic purposes. |
